4,547 results on '"Angiogenesis Inducing Agents"'
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2. Does the use of angiogenic biomarkers for the management of preeclampsia and fetal growth restriction improve outcomes?: Challenging the current status quo.
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Ramirez Zegarra, Ruben, Ghi, Tullio, and Lees, Christoph
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FETAL growth retardation , *PLACENTAL growth factor , *PREMATURE labor , *CHRONIC kidney failure , *PREGNANT women - Abstract
• Angiogenic biomarkers are important tools for the early prediction and diagnosis of preeclampsia. • Data from intervention trials do not support using angiogenic biomarkers for monitoring progressing of preeclampsia or deciding the timing of delivery. • There is insufficient evidence to recommend angiogenic biomarkers as an alternative to Doppler for surveillance and timing of delivery in fetal growth restriction. • Angiogenic biomarkers may have help differentiate between hypertension in chronic kidney disease from superimposed preeclampsia in pregnant women. Monitoring and timing of delivery in preterm preeclampsia and fetal growth restriction is one of the biggest challenges in Obstetrics. Finding the optimal time of delivery of these fetuses usually involves a trade-off between the severity of the disease and prematurity. So far, most clinical guidelines recommend the use of a combination between clinical, laboratory and ultrasound markers to guide the time of delivery. Angiogenic biomarkers, especially placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), have gained significant attention in recent years for their potential role in the prediction and diagnosis of placenta-related disorders including preeclampsia and fetal growth restriction. Another potential clinical application of the angiogenic biomarkers is for the differential diagnosis of patients with chronic kidney disease, as this condition shares similar clinical features with preeclampsia. Consequently, angiogenic biomarkers have been advocated as tools for monitoring and deciding the optimal time of the delivery of fetuses affected by placental dysfunction. In this clinical opinion, we critically review the available literature on PlGF and sFlt-1 for the surveillance and time of the delivery in fetuses affected by preterm preeclampsia and fetal growth restriction. Moreover, we explore the use of angiogenic biomarkers for the differentiation between chronic kidney disease and superimposed preeclampsia. [ABSTRACT FROM AUTHOR]
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- 2024
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3. 中药抑制肝细胞癌血管生成的作用机制.
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李香香, 王 振, 杨 星, and 李素领
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Angiogenesis is a key process in the development and progression of hepatocellular carcinoma (HCC) and can provide essential material conditions for the proliferation, invasion, and metastasis of HCC cells. Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy. Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways, enhancing efficacy and reducing toxicity, improving tumor prognosis, and prolonging survival time. Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors, upregulating the levels of anti-angiogenic factors, inhibiting endothelial cell proliferation, reducing the microvascular density of HCC tissue, and regulating related signaling pathways, and therefore, traditional Chinese medicine has unique advantages in the treatment of HCC. By summarizing related articles in China and globally in recent years, this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis, in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Lipopolysaccharides from Porphyromonas endodontalis and Porphyromonas gingivalis promote angiogenesis via Toll‐like‐receptors 2 and 4 pathways in vitro.
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Fernández, Alejandra, Herrera, Daniela, Hoare, Anilei, Hernández, Marcela, and Torres, Vicente A.
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PORPHYROMONAS gingivalis , *NEOVASCULARIZATION , *CELL migration , *VASCULAR endothelial growth factors , *PERIAPICAL periodontitis - Abstract
Aim: Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis‐related effects in vitro via TLR2 and TLR4. Methodology: Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL‐6 and VEGF‐A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP). Results: The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre‐treatment with anti‐TLR2 and anti‐TLR4 antibodies prevented P. endodontalis LPS‐induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p‐FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR‐2 and ‐4‐dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL‐6 and VEGF‐A synthesis in endothelial cells. TLR2 and TLR4 were required for IL‐6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL‐6 secretion by the other LPS. Finally, VEGF‐A synthesis did not require TLR signalling. Conclusion: Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Microglia-Derived Olfactomedin-like 3 Is a Potent Angiogenic Factor in Primary Mouse Brain Endothelial Cells: A Novel Target for Glioblastoma
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Joseph, Laila M, Toedebusch, Ryan G, Debebe, Eshetu, Bastian, Aurelie H, Lucchesi, Christopher A, Syed-Quadri, Shafee, Wittenburg, Luke A, Chen, Xinbin, Meyers, Frederick J, and Toedebusch, Christine M
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Biochemistry and Cell Biology ,Biological Sciences ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Microbiology ,Neurosciences ,Rare Diseases ,Brain Cancer ,Brain Disorders ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Mice ,Humans ,Vascular Endothelial Growth Factor A ,Endothelial Cells ,Angiogenesis Inducing Agents ,Glioblastoma ,Neovascularization ,Pathologic ,Vascular Endothelial Growth Factors ,Culture Media ,Conditioned ,Brain ,Brain Neoplasms ,Glycoproteins ,Intercellular Signaling Peptides and Proteins ,angiogenesis ,glioblastoma ,microglia ,cancer ,central nervous system ,C57Bl ,mice ,C57Bl/6 mice ,Other Chemical Sciences ,Genetics ,Other Biological Sciences ,Chemical Physics ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Neoangiogenesis, a hallmark feature of all malignancies, is robust in glioblastoma (GBM). Vascular endothelial growth factor (VEGF) has long been regarded as the primary pro-angiogenic molecule in GBM. However, anti-VEGF therapies have had little clinical efficacy, highlighting the need to explore VEGF-independent mechanisms of neoangiogenesis. Olfactomedin-like 3 (OLFML3), a secreted glycoprotein, is an established proangiogenic factor in many cancers, but its role in GBM neoangiogenesis is unknown. To gain insight into the role of OLFML3 in microglia-mediated angiogenesis, we assessed endothelial cell (EC) viability, migration and differentiation following (1) siRNA knockdown targeting endogenous EC Olfml3 and (2) EC exposure to human recombinant OLFML3 (rhOLFML3; 10 ng/mL, 48 h), and conditioned medium (CM) from isogenic control and Olfml3−/− microglia (48 h). Despite a 70% reduction in Olfml3 mRNA levels, EC angiogenic parameters were not affected. However, exposure to both rhOLFML3 and isogenic control microglial CM increased EC viability (p < 0.01), migration (p < 0.05) and differentiation (p < 0.05). Strikingly, these increases were abolished, or markedly attenuated, following exposure to Olfml3−/− microglial CM despite corresponding increased microglial secretion of VEGF-A (p < 0.0001). Consistent with reports in non-CNS malignancies, we have demonstrated that OLFML3, specifically microglia-derived OLFML3, promotes VEGF-independent angiogenesis in primary brain microvascular ECs and may provide a complementary target to mitigate neovascularization in GBM.
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- 2022
6. Angiogenesis
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Das, Joe M and Das, Joe M
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- 2023
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7. First Trimester Placental Assessment in the Screening of Preeclampsia and Intrauterine Growth Restriction
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Spanish Clinical Research Network - SCReN
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- 2022
8. Transition metals in angiogenesis – A narrative review
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Johannes Dürig, Maurizio Calcagni, and Johanna Buschmann
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Transition metals ,Angiogenesis inducing agents ,Angiogenesis inhibitors ,Vascular endothelial growth factors ,Reactive oxygen species ,Nanoparticles ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The aim of this paper is to offer a narrative review of the literature regarding the influence of transition metals on angiogenesis, excluding lanthanides and actinides. To our knowledge there are not any reviews up to date offering such a summary, which inclined us to write this paper. Angiogenesis describes the process of blood vessel formation, which is an essential requirement for human growth and development. When the complex interplay between pro- and antiangiogenic mediators falls out of balance, angiogenesis can quickly become harmful. As it is so fundamental, both its inhibition and enhancement take part in various diseases, making it a target for therapeutic treatments. Current methods come with limitations, therefore, novel agents are constantly being researched, with metal agents offering promising results. Various transition metals have already been investigated in-depth, with studies indicating both pro- and antiangiogenic properties, respectively. The transition metals are being applied in various formulations, such as nanoparticles, complexes, or scaffold materials. Albeit the increasing attention this field is receiving, there remain many unanswered questions, mostly regarding the molecular mechanisms behind the observed effects. Notably, approximately half of all the transition metals have not yet been investigated regarding potential angiogenic effects. Considering the promising results which have already been established, it should be of great interest to begin investigating the remaining elements whilst also further analyzing the established effects.
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- 2023
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9. Circulating miRNA-373 and Vascular Endothelial Growth Factor as Potential Biomarkers for Early Detection of Breast Cancer
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Raheem, Anmar R., Abdul-Rasheed, Omar F., Khattab, Omar S., Alsammarraie, Ahmed Z., Al-Aubaidy, Hayder, and Abid, Hussein A.
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- 2024
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10. Enhanced Stromal Cell CBS-H2S Production Promotes Estrogen-Stimulated Human Endometrial Angiogenesis.
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Qi, Qian-Rong, Lechuga, Thomas J, Patel, Basari, Nguyen, Nicole A, Yang, Yi-Hua, Li, Yan, Sarnthiyakul, Sassi, Zhang, Quan-Wei, Bai, Jin, Makhoul, Josh, and Chen, Dong-Bao
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Estrogen ,Clinical Research ,Adult ,Aged ,Angiogenesis Inducing Agents ,Cells ,Cultured ,Cystathionine beta-Synthase ,Endometrium ,Estradiol ,Female ,Humans ,Hydrogen Sulfide ,Menstrual Cycle ,Middle Aged ,Neovascularization ,Physiologic ,Postmenopause ,Pregnancy ,Stromal Cells ,Up-Regulation ,estrogens ,H2S ,angiogenesis ,endometrium ,women ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Endocrinology & Metabolism ,Bioinformatics and computational biology ,Medical biochemistry and metabolomics - Abstract
Angiogenesis is a physiological process for endometrial regeneration in the menstrual cycle and remodeling during pregnancy. Endogenous hydrogen sulfide (H2S), produced by cystathionine-β synthase (CBS) and cystathionine-γ lyase (CSE), is a potent proangiogenic factor; yet, whether the H2S system is expressed in the endometrium and whether H2S plays a role in endometrial angiogenesis are unknown. This study was to test whether estrogens stimulate endometrial H2S biosynthesis to promote endometrial microvascular endothelial cell (EMEC) angiogenesis. CBS messenger RNA/protein and H2S production significantly differed among endometria from postmenopausal (POM), premenopausal secretory (sPRM), and proliferative (pPRM) nonpregnant (NP) and pregnant (Preg) women (P < .05) in a rank order of POM approximately equal to sPRM is less than pPRM is less than Preg, positively correlating with angiogenesis indices and endogenous estrogens and with no difference in CSE expression. CBS and CSE proteins were localized to stroma, glands, and vessels in endometrium, and greater stromal CBS protein was observed in the pPRM and Preg states. Estradiol-17β (E2) (but not progesterone) stimulated CBS (but not CSE) expression and H2S production in pPRM endometrial stromal cells (ESCs) in vitro, which were attenuated by ICI 182 780. The H2S donor sodium hydrosulfide promoted in vitro EMEC angiogenesis. Co-culture with sPRM, pPRM, and Preg ESCs all stimulated EMEC migration with a rank order of sPRM less than pPRM approximately equal to Preg. CBS (but not CSE) inhibition attenuated ESC-stimulated EMEC migration. E2 did not affect EMEC migration but potentiated ESC-stimulated EMEC migration. Altogether, estrogens stimulate specific receptor-dependent stromal CBS-H2S production to promote endometrial EMEC angiogenesis in women.
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- 2020
11. Suppressing neutrophil-dependent angiogenesis abrogates resistance to anti-VEGF antibody in a genetic model of colorectal cancer
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Itatani, Yoshiro, Yamamoto, Takamasa, Zhong, Cuiling, Molinolo, Alfredo A, Ruppel, Jane, Hegde, Priti, Taketo, M Mark, and Ferrara, Napoleone
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Colo-Rectal Cancer ,Digestive Diseases ,Aetiology ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Development of treatments and therapeutic interventions ,Angiogenesis Inducing Agents ,Animals ,Antibodies ,Colonic Neoplasms ,Colorectal Neoplasms ,Female ,Granulocyte Colony-Stimulating Factor ,Liver Neoplasms ,Male ,Mice ,Mice ,Inbred C57BL ,Models ,Genetic ,Myeloid Cells ,Neovascularization ,Pathologic ,Neutrophils ,Vascular Endothelial Growth Factor A ,colorectal cancer ,angiogenesis ,inflammation ,myeloid cells ,drug resistance - Abstract
We tested cis-ApcΔ716/Smad4+/- and cis-ApcΔ716/Smad4+/-KrasG12D mice, which recapitulate key genetic abnormalities accumulating during colorectal cancer (CRC) tumorigenesis in humans, for responsiveness to anti-VEGF therapy. We found that even tumors in cis-ApcΔ716/Smad4+/-KrasG12D mice, although highly aggressive, were suppressed by anti-VEGF treatment. We tested the hypothesis that inflammation, a major risk factor and trigger for CRC, may affect responsiveness to anti-VEGF. Chemically induced colitis (CIC) in cis-ApcΔ716/Smad4+/- and cis-ApcΔ716/Smad4+/-KrasG12D mice promoted development of colon tumors that were largely resistant to anti-VEGF treatment. The myeloid growth factor G-CSF was markedly increased in the serum after induction of colitis. Antibodies blocking G-CSF, or its target Bv8/PROK2, suppressed tumor progression and myeloid cell infiltration when combined with anti-VEGF in CIC-associated CRC and in anti-VEGF-resistant CRC liver metastasis models. In a series of CRC specimens, tumor-infiltrating neutrophils strongly expressed Bv8/PROK2. CRC patients had significantly higher plasma Bv8/PROK2 levels than healthy volunteers and high plasma Bv8/PROK2 levels were inversely correlated with overall survival. Our findings establish Bv8/PROK2 as a translational target in CRC, in combination with anti-VEGF agents.
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- 2020
12. Nonmuscle myosin 2 regulates cortical stability during sprouting angiogenesis.
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Ma, Xuefei, Uchida, Yutaka, Wei, Tingyi, Liu, Chengyu, Adams, Ralf, Kubota, Yoshiaki, Gutkind, J, Mukouyama, Yoh-Suke, and Adelstein, Robert
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Angiogenesis Inducing Agents ,Animals ,Collagen ,Cytoskeletal Proteins ,Endothelial Cells ,Mice ,Mice ,Knockout ,Morphogenesis ,Myosin Heavy Chains ,Myosin Type II ,Neovascularization ,Physiologic ,Nonmuscle Myosin Type IIA ,Nonmuscle Myosin Type IIB ,Signal Transduction ,rho-Associated Kinases - Abstract
Among the three nonmuscle myosin 2 (NM2) paralogs, NM 2A and 2B, but not 2C, are detected in endothelial cells. To study the role of NM2 in vascular formation, we ablate NM2 in endothelial cells in mice. Ablating NM2A, but not NM2B, results in reduced blood vessel coverage and increased vascular branching in the developing mouse skin and coronary vasculature. NM2B becomes essential for vascular formation when NM2A expression is limited. Mice ablated for NM2B and one allele of NM2A develop vascular abnormalities similar to those in NM2A ablated mice. Using the embryoid body angiogenic sprouting assay in collagen gels reveals that NM2A is required for persistent angiogenic sprouting by stabilizing the endothelial cell cortex, and thereby preventing excessive branching and ensuring persistent migration of the endothelial sprouts. Mechanistically, NM2 promotes focal adhesion formation and cortical protrusion retraction during angiogenic sprouting. Further studies demonstrate the critical role of Rho kinase-activated NM2 signaling in the regulation of angiogenic sprouting in vitro and in vivo.
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- 2020
13. Epoxyeicosatrienoic acid (EET)-stimulated angiogenesis is mediated by epoxy hydroxyeicosatrienoic acids (EHETs) formed from COX-2
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Rand, Amy A, Rajamani, Anita, Kodani, Sean D, Harris, Todd R, Schlatt, Lukas, Barnych, Bodgan, Passerini, Anthony G, and Hammock, Bruce D
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Cardiovascular ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Angiogenesis Inducing Agents ,Cyclooxygenase 2 ,Cycloparaffins ,Eicosanoids ,Endothelial Cells ,Humans ,Receptors ,Vascular Endothelial Growth Factor ,arachidonic acid ,endothelial cells ,cyclooxygenase 2 ,mass spectrometry ,cancer ,metabolism ,soluble epoxide hydrolase ,angiogenesis ,Medical Biochemistry and Metabolomics ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical biochemistry and metabolomics - Abstract
Epoxyeicosatrienoic acids (EETs) are formed from the metabolism of arachidonic acid by cytochrome P450s. EETs promote angiogenesis linked to tumor growth in various cancer models that is attenuated in vivo by cyclooxygenase 2 (COX-2) inhibitors. This study further defines a role for COX-2 in mediating endothelial EET metabolism promoting angiogenesis. Using human aortic endothelial cells (HAECs), we quantified 8,9-EET-induced tube formation and cell migration as indicators of angiogenic potential in the presence and absence of a COX-2 inducer [phorbol 12,13-dibutyrate (PDBu)]. The angiogenic response to 8,9-EET in the presence of PDBu was 3-fold that elicited by 8,9-EET stabilized with a soluble epoxide hydrolase inhibitor (t-TUCB). Contributing to this response was the COX-2 metabolite of 8,9-EET, the 11-hydroxy-8,9-EET (8,9,11-EHET), which exogenously enhanced angiogenic responses in HAECs at levels comparable to those elicited by vascular endothelial growth factor (VEGF). In contrast, the 15-hydroxy-8,9-EET isomer was also formed but inactive. The 8,9,11-EHET also promoted expression of the VEGF family of tyrosine kinase receptors. These results indicate that 8,9-EET-stimulated angiogenesis is enhanced by COX-2 metabolism in the endothelium through the formation of 8,9,11-EHET. This alternative pathway for the metabolism of 8,9-EET may be particularly important in regulating angiogenesis under circumstances in which COX-2 is induced, such as in cancer tumor growth and inflammation.
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- 2019
14. Ginsenoside Rg1 regulates astrocytes to promote angiogenesis in spinal cord injury via the JAK2/STAT3 signaling pathway.
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Yin, Shiyuan, Xia, Feiyun, Zou, Wenjun, Jiang, Fengxian, Shen, Kelv, Sun, Baihan, and Lu, Zhengfeng
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OXYGEN metabolism , *GLUCOSE metabolism , *CHINESE medicine , *BIOLOGICAL models , *MOTOR ability , *WOUND healing , *SMALL interfering RNA , *IN vitro studies , *VASCULAR endothelial growth factors , *INTRAPERITONEAL injections , *NEUROGLIA , *HERBAL medicine , *EVOKED potentials (Electrophysiology) , *PHARMACEUTICAL chemistry , *CELL proliferation , *SPINAL cord injuries , *CELLULAR signal transduction , *FLUORESCENT antibody technique , *FUNCTIONAL status , *JANUS kinases , *RATS , *IMMUNOHISTOCHEMISTRY , *ANIMAL experimentation , *WESTERN immunoblotting , *ENDOTHELIAL cells , *GINSENG , *NEOVASCULARIZATION - Abstract
Ginseng (Panax ginseng C. A. Mey) is a common traditional Chinese medicine used for anti-inflammation, anti-apoptosis, anti-oxidative stress, and neuroprotection. Ginsenosides Rg1, the main active components isolated from ginseng, may be a feasible therapy for spinal cord injury (SCI). SCI causes endothelial cell death and blood vessel rupture, ultimately resulting in long-term neurological impairment. As a result, encouraging spinal angiogenesis may be a feasible therapy for SCI. This investigation aimed to validate the capacity of ginsenoside Rg1 in stimulating angiogenesis within the spinal cord. Rats with SCI were injected intraperitoneally with ginsenoside Rg1. The effectiveness of ginsenoside Rg1 was assessed using the motor function score and the motor-evoked potential (MEP). Immunofluorescence techniques were applied to identify the spinal cord's angiogenesis. Angiogenic factors were examined through Western Blot (WB) and Immunohistochemistry. Oxygen-glucose deprivation (OGD) was employed to establish the hypoxia-ischemia model in vitro, and astrocytes (As) were given ginsenoside Rg1 and co-cultured with spinal cord microvascular endothelial cells (SCMECs). Immunofluorescence, wound healing test, and tube formation assay were used to identify the co-cultured SCMECs' activity. Finally, network pharmacology analysis and siRNA transfection were applied to verify the mechanism of ginsenoside Rg1 promoting angiogenesis. The rats with SCI treated with ginsenoside Rg1 indicated more significant functional recovery, more pronounced angiogenesis, and higher levels of angiogenic factor expression. In vitro, the co-culture system with ginsenoside Rg1 intervention improved SCMECs' capacity for proliferating, migrating, and forming tubes, possibly by promoting the expression of vascular endothelial growth factor (VEGF) in As via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Ginsenoside Rg1 can regulate As to promote angiogenesis, which may help to understand the mechanism of promoting SCI recovery. Schematic illustration of the role of ginsenoside Rg1 in promoting angiogenesis during spinal cord injury. Ginsenoside Rg1 modulates the activity of astrocytes, promoting the secretion of VEGF via the JAK2/STAT3 pathway. This up-regulated expression of VEGF by astrocytes has a subsequent effect on spinal microvascular endothelial cells, leading to enhanced proliferation, migration, and tubulation of these cells, ultimately contributing to angiogenesis in spinal cord injury. [Display omitted] • Ginsenoside Rg1 can be used as a potential therapeutic agent for effective treatment of spinal cord injury. • Ginsenoside Rg1 regulates astrocytes to promote angiogenesis in spinal cord injury. • JAK2-STAT3 is a key signaling pathway for angiogenesis in spinal cord injury. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis
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Chen, Dong-Bao, Feng, Lin, Hodges, Jennifer K, Lechuga, Thomas J, and Zhang, Honghai
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Cardiovascular ,Angiogenesis Inducing Agents ,Animals ,Arteries ,Cell Differentiation ,Cell Line ,Cell Movement ,Cell Proliferation ,Coculture Techniques ,Cystathionine beta-Synthase ,Cystathionine gamma-Lyase ,Endothelial Cells ,Female ,Humans ,Hydrogen Sulfide ,MAP Kinase Signaling System ,Mitogen-Activated Protein Kinases ,Nitric Oxide Synthase Type III ,Placenta ,Pregnancy ,Proto-Oncogene Proteins c-akt ,Sheep ,Trophoblasts ,angiogenesis ,endothelial cells ,human ,hydrogen sulfide ,placenta ,trophoblasts ,Biological Sciences ,Medical and Health Sciences ,Obstetrics & Reproductive Medicine - Abstract
Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1.
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- 2017
16. Shexiang Baoxin pills promotes angiogenesis in myocardial infarction rats via up-regulation of 20-HETE-mediated endothelial progenitor cells mobilization
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Huang, Feifei, Liu, Yang, Yang, Xia, Che, Di, Qiu, Kaifeng, Hammock, Bruce D, Wang, Jingfeng, Wang, Mong-Heng, Chen, Jie, and Huang, Hui
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Medical Physiology ,Biomedical and Clinical Sciences ,Cardiovascular ,Heart Disease ,Regenerative Medicine ,Stem Cell Research ,Heart Disease - Coronary Heart Disease ,Amidines ,Angiogenesis Inducing Agents ,Animals ,Cytochrome P-450 Enzyme Inhibitors ,Disease Models ,Animal ,Drugs ,Chinese Herbal ,Endothelial Progenitor Cells ,Hydroxyeicosatetraenoic Acids ,Male ,Myocardial Infarction ,Myocardium ,Neovascularization ,Physiologic ,Rats ,Sprague-Dawley ,Signal Transduction ,Vascular Endothelial Growth Factor A ,Shexiang Baoxin pills ,20-HETE ,Endothelial progenitor cells ,Vascular endothelial growth factor ,Angiogenesis ,Myocardial infarction ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Background and aimsTherapeutic angiogenesis is a pivotal strategy for ischemic heart disease. The aim of the present study was to determine the effect and molecular mechanism of Shexiang Baoxin pills, a widely-used traditional Chinese medicine for ischemic heart disease, on angiogenesis in a rat model of myocardial infarction (MI).MethodsWe used the occlusion of left anterior descending coronary artery of Sprague-Dawley rats as a model of MI. The MI rats were treated with distilled water, Shexiang Baoxin pills, or Shexiang Baoxin pills + HET0016 (a selective blocker of the biosynthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) at 10 mg/kg/day), respectively. Sham-operated rats were used as controls.ResultsTreatment with Shexiang Baoxin pills increases the level of serum 20-HETE in MI rats, which can be suppressed by HET0016 treatment. Shexiang Baoxin pills shows cardio-protective effects on MI rats, including improving cardiac function, decreasing infarction area, and promoting angiogenesis in peri-infarct area. The protective effects of Shexiang Baoxin pills are partly inhibited by HET0016. Furthermore, Shexiang Baoxin pills enhances the number of circulating endothelial progenitor cells (EPCs) and the expression of the vascular endothelial growth factor (VEGF), based on immunohistochemical analysis, in peri-infarct area of MI rats, which is partly suppressed by HET0016.ConclusionsShexiang Baoxin pills may partially participate in angiogenesis in MI rats. The protective mechanism of Shexiang Baoxin pills may be mediated via up-regulation of 20-HETE, which promotes EPCs mobilization and VEGF expression.
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- 2017
17. Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids
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Rand, Amy A, Barnych, Bogdan, Morisseau, Christophe, Cajka, Tomas, Lee, Kin Sing Stephen, Panigrahy, Dipak, and Hammock, Bruce D
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Organic Chemistry ,Chemical Sciences ,Cancer ,8 ,11 ,14-Eicosatrienoic Acid ,Angiogenesis Inducing Agents ,Arachidonic Acid ,Cyclooxygenase 1 ,Cyclooxygenase 2 ,Humans ,omega-6 fatty acids ,epoxyeicosatrienoic acids ,metabolism ,cyclooxygenase ,angiogenesis - Abstract
Arachidonic acid (ARA) is metabolized by cyclooxygenase (COX) and cytochrome P450 to produce proangiogenic metabolites. Specifically, epoxyeicosatrienoic acids (EETs) produced from the P450 pathway are angiogenic, inducing cancer tumor growth. A previous study showed that inhibiting soluble epoxide hydrolase (sEH) increased EET concentration and mildly promoted tumor growth. However, inhibiting both sEH and COX led to a dramatic decrease in tumor growth, suggesting that the contribution of EETs to angiogenesis and subsequent tumor growth may be attributed to downstream metabolites formed by COX. This study explores the fate of EETs with COX, the angiogenic activity of the primary metabolites formed, and their subsequent hydrolysis by sEH and microsomal EH. Three EET regioisomers were found to be substrates for COX, based on oxygen consumption and product formation. EET substrate preference for both COX-1 and COX-2 were estimated as 8,9-EET > 5,6-EET > 11,12-EET, whereas 14,15-EET was inactive. The structure of two major products formed from 8,9-EET in this COX pathway were confirmed by chemical synthesis: ct-8,9-epoxy-11-hydroxy-eicosatrienoic acid (ct-8,9-E-11-HET) and ct-8,9-epoxy-15-hydroxy-eicosatrienoic acid (ct-8,9-E-15-HET). ct-8,9-E-11-HET and ct-8,9-E-15-HET are further metabolized by sEH, with ct-8,9-E-11-HET being hydrolyzed much more slowly. Using an s.c. Matrigel assay, we showed that ct-8,9-E-11-HET is proangiogenic, whereas ct-8,9-E-15-HET is not active. This study identifies a functional link between EETs and COX and identifies ct-8,9-E-11-HET as an angiogenic lipid, suggesting a physiological role for COX metabolites of EETs.
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- 2017
18. Correlation Between Optic Nerve Vessel Anomalies, Serum Angiogenic Factors and Renal Anomalies in Down Syndrome Children (DOPANUR)
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- 2018
19. Angiogenesis of Extracted Tooth Wound on Wistar Rats After Application of Okra (Abelmoschus esculentus) Gel Extract
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Muhammad Luthfi, Wisnu Setyari Juliastuti, and Yuniar Aliyah Risky
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Tooth Extraction ,Wound Healing ,Angiogenesis Inducing Agents ,Dentistry ,RK1-715 - Abstract
Objective: To analyze angiogenesis in the post-extracted tooth of Wistar rats after application of okra (Abelmoschus esculentus) extract. Material and Methods: A total of 18 rats were divided into two groups (control and treatment). Okra extract with a concentration of 30% in gel form was applied on the post- extraction socket of the treatment group. The rats were sacrificed on day-3, day-5, and day-7 after tooth extraction. The newly-formed blood vessels were counted and statistically analyzed by means of One Way ANOVA and Tukey HSD with a significance level set at 5%. Results: The newly-formed capillaries of the control group (4.67 ± 1.53) on day-3 were lower than the treatment group (9.00 ± 1.00). The newly-formed capillaries recorded from the control group, both in day-5 (9.33 ± 1.53) and day-7 (8.67 ± 1.53) were lower than the treatment group, which started to decreased from day-5 (13.67 ± 1.53) to day-7 (12.33 ± 0.58). Significant differences were found in treatment group, on day-3 compared to day-5 (p=0.005), and on day-3 to day-7 (p=0.024). Conclusion: Okra extract in gel form at 30% concentration can increase the angiogenesis during the wound healing process of the extracted tooth on Wistar rats.
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- 2022
20. Skin graft associated with platelet-rich plasma in correcting extensive injuries resulting from the resection of skin cancer chemically induced in rats
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Josiane Morais Pazzini, Stella Habib Moreira, Pedro Cassino, Marjury Maronezi, Michelle Zangirolami, Jorge Luis Alvaréz Gomés, Paulo Henrique Bertolo, Michelle do Carmo Pereira Rocha, Sonia Prince Fiebi, Caroline Kajiura, Filippo Janoni Bernardes, Caio Bustamante, and Andrigo Barboza De Nardi
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Angiogenesis Inducing Agents ,Granulation Tissue ,Platelet-Rich Plasma ,Skin Transplantation ,Surgical Flaps ,Rats ,Surgery ,RD1-811 - Abstract
ABSTRACT Purpose: To evaluate whether using platelet-rich plasma (PRP) in the graft recipient bed after the resection of a neoplasia can influence its recurrence because this product stimulates angiogenesis, mitogenesis and chemotaxis. Methods: A study with 30 rats Wistar (Rattus norvegicus albinus), which were separated into group A (induction of carcinogenesis, PRP in the postoperative period) and group B (induction of carcinogenesis, absence of PRP in the postoperative period), with 15 animals in each. Carcinogenesis was induced on the skin of the animals’ chest by the topical application of 0.5% dimethylbenzantracene (DMBA) diluted in acetone. After surgical resection of the induced neoplasia, PRP was used to stimulate angiogenesis before surgical wound synthesis. Data on the control and experimental groups and macroscopic and microscopic variables were evaluated using analysis of variance and the Tukey’s test (5%). Results: It was possible to determine that the use of PRP is good in reconstructive surgeries, but it is contraindicated in patients during tumor resection, as it can cause changes in the surgical bed, in addition to stimulating recurrences and metastases. Conclusions: PRP may interact with tumour cells that were in the recipient site of the surgical wound during the resection of a neoplasia, and a local recurrence process can be triggered by applying this product.
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- 2022
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21. Evidence for Pro-angiogenic Functions of VEGF-Ax
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Xin, Hong, Zhong, Cuiling, Nudleman, Eric, and Ferrara, Napoleone
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,1.1 Normal biological development and functioning ,Underpinning research ,Cardiovascular ,Alternative Splicing ,Amino Acid Sequence ,Angiogenesis Inducing Agents ,Angiogenesis Inhibitors ,Animals ,Capillary Permeability ,Chemotaxis ,Cloning ,Molecular ,Endothelial Cells ,Guinea Pigs ,HEK293 Cells ,Humans ,Mice ,Mitogens ,Mitosis ,Neovascularization ,Physiologic ,Neuropilin-1 ,Protein Biosynthesis ,Protein Isoforms ,RNA ,Messenger ,Recombinant Proteins ,Tyrosine ,Vascular Endothelial Growth Factor A ,Vascular Endothelial Growth Factor Receptor-1 ,Vascular Endothelial Growth Factor Receptor-2 ,VEGF ,angiogenesis ,endothelium ,readthrough translation ,tyrosine kinase ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
The VEGF-A isoforms play a crucial role in vascular development, and the VEGF signaling pathway is a clinically validated therapeutic target for several pathological conditions. Alternative mRNA splicing leads to the generation of multiple VEGF-A isoforms, including VEGF165. A recent study reported the presence of another isoform, VEGF-Ax, arising from programmed readthrough translation. Compared to VEGF165, VEGF-Ax has a 22-amino-acid extension in the COOH terminus and has been reported to function as a negative regulator of VEGF signaling in endothelial cells, with potent anti-angiogenic effects. Here, we show that, contrary to the earlier report, VEGF-Ax stimulates endothelial cell mitogenesis, angiogenesis, as well as vascular permeability. Accordingly, VEGF-Ax induces phosphorylation of key tyrosine residues in VEGFR-2. Notably, VEGF-Ax was less potent than VEGF165, consistent with its impaired binding to the VEGF co-receptor neuropilin-1.
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- 2016
22. A Comprehensive Review of the Efficacy and Safety of Dopamine Agonists for Women with Endometriosis-associated Infertility from Inception to July 31, 2022.
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Estole-Casanova LA
- Abstract
Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted., Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility., Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures., Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data., Conclusion: Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility., Competing Interests: The author declared no conflicts of interest., (© 2024 Acta Medica Philippina.)
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- 2024
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23. Thymic Stromal Lymphopoietin (TSLP) Is Cleaved by Human Mast Cell Tryptase and Chymase.
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Canè L, Poto R, Palestra F, Iacobucci I, Pirozzi M, Parashuraman S, Ferrara AL, Illiano A, La Rocca A, Mercadante E, Pucci P, Marone G, Spadaro G, Loffredo S, Monti M, and Varricchi G
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- Humans, Tryptases, Chymases, Angiogenesis Inducing Agents, Serine Proteases, Cytokines, Thymic Stromal Lymphopoietin, Asthma
- Abstract
Thymic stromal lymphopoietin (TSLP), mainly expressed by epithelial cells, plays a central role in asthma. In humans, TSLP exists in two variants: the long form TSLP (lfTSLP) and a shorter TSLP isoform (sfTSLP). Macrophages (HLMs) and mast cells (HLMCs) are in close proximity in the human lung and play key roles in asthma. We evaluated the early proteolytic effects of tryptase and chymase released by HLMCs on TSLP by mass spectrometry. We also investigated whether TSLP and its fragments generated by these enzymes induce angiogenic factor release from HLMs. Mass spectrometry (MS) allowed the identification of TSLP cleavage sites caused by tryptase and chymase. Recombinant human TSLP treated with recombinant tryptase showed the production of 1-97 and 98-132 fragments. Recombinant chymase treatment of TSLP generated two peptides, 1-36 and 37-132. lfTSLP induced the release of VEGF-A, the most potent angiogenic factor, from HLMs. By contrast, the four TSLP fragments generated by tryptase and chymase failed to activate HLMs. Long-term TSLP incubation with furin generated two peptides devoid of activating property on HLMs. These results unveil an intricate interplay between mast cell-derived proteases and TSLP. These findings have potential relevance in understanding novel aspects of asthma pathobiology.
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- 2024
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24. Preeclampsia at term: evidence of disease heterogeneity based on the profile of circulating cytokines and angiogenic factors.
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Chaiworapongsa T, Romero R, Gomez-Lopez N, Suksai M, Gallo DM, Jung E, Berry SM, Awonuga A, Tarca AL, and Bryant DR
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- Pregnancy, Female, Humans, Placenta Growth Factor, Cytokines, Case-Control Studies, Angiogenesis Inducing Agents, Biomarkers, Inflammation, Monocyte Chemoattractant Proteins, Vascular Endothelial Growth Factor Receptor-1, Pre-Eclampsia
- Abstract
Background: Intravascular inflammation and an antiangiogenic state have been implicated in the pathophysiology of preeclampsia. On the basis of the profiles of their angiogenic/antiangiogenic factors, women with preeclampsia at term may be classified into 2 subgroups with different characteristics and prevalence of adverse outcomes. This study was undertaken to examine whether these 2 subgroups of preeclampsia at term also show differences in their profiles of intravascular inflammation., Objective: This study aimed to determine the plasma profiles of cytokines and chemokines in women with preeclampsia at term who had a normal or an abnormal angiogenic profile., Study Design: A nested case-control study was conducted to include women classified into 3 groups: women with an uncomplicated pregnancy (n=213) and women with preeclampsia at term with a normal (n=55) or an abnormal (n=41) angiogenic profile. An abnormal angiogenic profile was defined as a plasma ratio of placental growth factor and soluble fms-like tyrosine kinase-1 multiple of the median <10th percentile for gestational age. Concentrations of cytokines were measured by multiplex immunoassays., Results: Women with preeclampsia at term and an abnormal angiogenic profile showed evidence of the greatest intravascular inflammation among the study groups. These women had higher plasma concentrations of 5 cytokines (interleukin-6, interleukin-8, interleukin-12/interleukin-23p40, interleukin-15, and interleukin-16) and 7 chemokines (eotaxin, eotaxin-3, interferon-γ inducible protein-10, monocyte chemotactic protein-4, macrophage inflammatory protein-1β, macrophage-derived chemokine, and thymus and activation-regulated chemokine compared to women with an uncomplicated pregnancy. By contrast, women with preeclampsia at term and a normal angiogenic profile, compared to women with an uncomplicated pregnancy, had only a higher plasma concentration of monocyte chemotactic protein-4. A correlation between severity of the antiangiogenic state, blood pressure, and plasma concentrations of a subset of cytokines was observed., Conclusion: Term preeclampsia can be classified into 2 clusters. One is characterized by an antiangiogenic state coupled with an excessive inflammatory process, whereas the other has neither of these features. These findings further support the heterogeneity of preeclampsia at term and may explain the distinct clinical outcomes., (Published by Elsevier Inc.)
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- 2024
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25. Angiogenic potential of hypoxia preconditioned human adipose and umbilical cord-derived mesenchymal stem cells: a comparative study.
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PHAM, Viet Q., TRAN, Nhan N., VU, Binh T., LE, Hanh T., VU, Ngoc B., and PHAM, Phuc V.
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- *
NEOVASCULARIZATION , *HYPOXEMIA , *UMBILICAL cord , *MESENCHYMAL stem cells , *MULTIPOTENT stem cells - Abstract
BACKGROUND: Angiogenesis plays an important role in tissue repair. In recent years, one of the main research strategies used to induce angiogenesis in vivo has been via stem cell therapy, especially therapy using mesenchymal stem cells (MSCs). However, the use of MSCs in angiogenesis has also been limited due to the low angiogenic potency of MSCs. Therefore, this study aimed to investigate the effects of hypoxiapreconditioned MSCs from human adipose tissue-derived MSCs (AT -MSCs) and from human umbilical cord-derived MSCs (UC-MSCs). We evaluated the role of hypoxia on the angiogenic potency of these MSCs. METHODS: Both AT -MSCs and UC-MSCs were obtained from an established cell bank and expanded in vitro. After expansion, they were checked for their stemness before use in experiments. MSCs were preconditioned in a hypoxic environment (5% oxygen) for 48 hours. The concentrations of growth factors (such as HGF, bFGF, and VEGF) in the cell culture supernatants collected from culture media of the hypoxiapreconditioned AT -MSCs and UC-MSCs (as well as those from AT -MSCs and UC-MSCs cultured in normoxia) were measured by ELISA. Angiogenic potency-related gene expression markers (such as angiogenin, angiopoietin-1, angiopoietin-2, bFGF, HB-EGF, MMP-9, PDGF-BB, SDF-1 alpha, TGF-beta 1, VEGF, HGF, IL-6, and IL-8) of hypoxic- and normoxic-cultured AT -MSCs and UC-MSCs were evaluated using realtime reverse transcription PCR. In-vivo assessment of the angiogenic potency of hypoxic and normoxic AT -MSCs and UC-MSCs was conducted using an ex ovo quail embryo model (cultured in 6-well plates). The angiogenic potency was evaluated based on the area and length of blood vessels formed in the quail embryos on days 1, 3, 5, and 7 after transplantation with hypoxic AT -MSCs, normoxic AT -MSCs, hypoxic UC-MSCs, or normoxic UC-MSCs, and compared to placebo control (PBS injection). RESULTS: The data showed that preconditioning with hypoxia promoted the secretion of bFGF, VEGF, and HGF by both AT -MSCs and UCMSCs. For AT-MSCs, there was a significant increase in VEGF and bFGF production when preconditioned with hypoxia, compared to normoxia, while HGF production was only slightly increased. For UC-MSCs, there was a significant increase in bFGF and HGF production, but only a slight change in VEGF production when preconditioned with hypoxia, as compared to normoxia. A significant up-regulation of gene expression was observed for angiogenin, angiopoietin-1, angiopoietin-2, bFGF, HB-EGF, HGF, IL-8, MMP-9, PDGF-BB, SDF-1 alpha, TGF-beta 1, and VEGF in both hypoxic AT -MSCs and UC-MSCs, compared to normoxic AT -MSCs and UC-MSCs. In quail embryo models, normoxic UCMSCs promoted angiogenesis better than normoxic AT -MSCs; however, the angiogenic potency of hypoxic AT -MSCs and UC-MSCs were not significantly different. CONCLUSIONS: The angiogenic potency of UC-MSCs was better than that of AT -MSCs. However, when preconditioned with hypoxia (5% O2), the angiogenic potency of both AT -MSCs and UC-MSCs was similar. In vivo, hypoxic preconditioning could enhance the angiogenic potency of AT-MSCs, compared to normoxic AT-MSCs, although the angiogenic potency of hypoxic and normoxic UC-MSCs was not significantly different. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Glucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency
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Han, Christina S, Herrin, Melissa A, Pitruzzello, Mary C, Mulla, Melissa J, Werner, Erika F, Pettker, Christian M, Flannery, Clare A, and Abrahams, Vikki M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Diabetes ,Contraception/Reproduction ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Angiogenesis Inducing Agents ,Antigens ,CD ,Carrier Proteins ,Cell Line ,Cell Movement ,Chemokine CCL5 ,Chemokine CXCL1 ,Diabetes Complications ,Diabetes Mellitus ,Endoglin ,Female ,Glucose ,Granulocyte Colony-Stimulating Factor ,Humans ,Inflammation ,Interleukins ,Metformin ,NLR Family ,Pyrin Domain-Containing 3 Protein ,Placenta ,Pre-Eclampsia ,Pregnancy ,Pregnancy Trimester ,First ,Receptors ,Cell Surface ,Trophoblasts ,Uterus ,Vascular Endothelial Growth Factor Receptor-1 ,glucose ,metformin ,preeclampsia ,trophoblast - Abstract
ProblemDiabetes confers an increased risk of preeclampsia, but its pathogenic role in preeclampsia is poorly understood. The objective of this study was to elucidate the effects of excess glucose on trophoblast function and whether any changes could be reversed by metformin.Method of studyThe human first trimester trophoblast cell line (Sw.71) was treated with glucose at 5, 10, 25, and 50 mm, in the presence and absence of metformin. Trophoblast migration was quantified and supernatant cytokine, chemokine, and angiogenic factors measured.ResultsIncreasing concentrations of glucose significantly increased trophoblast secretion of the inflammatory cytokines/chemokines: IL-1β, IL-6, IL-8, GRO-α, RANTES, and G-CSF; significantly increased trophoblast secretion of the anti-angiogenic factors sFlt-1 and sEndoglin; and significantly decreased trophoblast migration. Excess glucose-induced trophoblast IL-1β production was inhibited by disabling the Nalp3/ASC inflammasome. Metformin partially reduced the glucose-induced inflammatory response, but had no effect on the anti-angiogenic or antimigratory response.ConclusionExcess glucose induced a pro-inflammatory, anti-angiogenic, and antimigratory state in first trimester trophoblast cells. Glucose-induced trophoblast IL-1β secretion was mediated by the inflammasome. Glucose-induced inflammation was partially reversed by metformin. These findings demonstrate the pleiotropic effects of hyperglycaemia on the trophoblast, providing potential explanations for the strong link between diabetes and preeclampsia.
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- 2015
27. Recombinant Human Erythropoietin Improves the Neurofunctional Recovery of Rats Following Traumatic Brain Injury via an Increase in Circulating Endothelial Progenitor Cells
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Wang, Liang, Wang, Xiaonan, Su, Hua, Han, Zhenying, Yu, Huijie, Wang, Dong, Jiang, Rongcai, Liu, Zhenlin, and Zhang, Jianning
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Stem Cell Research ,Traumatic Head and Spine Injury ,Physical Injury - Accidents and Adverse Effects ,Stem Cell Research - Nonembryonic - Human ,Brain Disorders ,Regenerative Medicine ,Traumatic Brain Injury (TBI) ,Angiogenesis Inducing Agents ,Animals ,Brain Injuries ,Endothelial Progenitor Cells ,Erythropoietin ,Hematocrit ,Hippocampus ,Humans ,Male ,Rats ,Rats ,Wistar ,Recombinant Proteins ,Recovery of Function ,Spatial Learning ,Traumatic brain injury ,Endothelial progenitor cells ,Angiogenesis ,Public Health and Health Services ,Clinical sciences - Abstract
Previous studies show that circulating endothelial progenitor cells (EPCs) promote angiogenesis, which is a process associated with improved recovery in animal models of traumatic brain injury (TBI), and that recombinant human erythropoietin (rhEPO) plays a protective role following stroke. Thus, it was hypothesized that rhEPO would enhance recovery following brain injury in a rat model of TBI via an increase in the mobilization of EPCs and, subsequently, in angiogenesis. Flow cytometry assays using CD34- and CD133-specific antibodies were utilized to identify alterations in EPC levels, CD31 and CD34 antibody-stained brain tissue sections were used to quantify angiogenesis, and the Morris water maze (MWM) test and the modified Neurological Severity Score (mNSS) test were used to evaluate behavioral recovery. Compared with saline treatment, treatment with rhEPO significantly increased the number of circulating EPCs on days 1, 4, 7, and 14 (P
- Published
- 2015
28. Effect of lysophosphatidic Acid on the Vascular Endothelial Growth Factor Expression in Autotransplanted Mouse Ovaries Encapsulated in Sodium Alginate
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Maryam Dehghan, Shirin Shahbazi, and Mojdeh Salehnia
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Angiogenesis Inducing Agents ,Autologous Transplantation ,Lysophosphatidic Acid ,Ovary ,Vascular Endothelial Growth Factors ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) supplementation during in vitro culture and transplantation of mouse ovaries on the follicular development and expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor at the mRNA and protein levels. Materials and methods: Three weeks old mice ovaries were cultured in the presence and absence of LPA for 24 hours, then they were capsulated in sodium alginate in the presence and absence of LPA as four experimental groups. After transplantation the vaginal smears were performed daily to evaluate the initiation of the estrous cycle. The morphology and follicular distribution were analyzed at the first and fourth estrous cycles using hematoxylin and eosin staining. Then in the groups that showed higher and lower follicular development the immunohistochemistry assay was conducted to identify VEGF protein expression, and the real time RT-PCR was done to analyze the expression of Vegf gene at the first estrus cycle. Results: The large size follicles and also the corpus luteum were prominent in all transplanted groups at fourth estrus cycle in comparison with intact control groups. The statistically lowest percentage of small size follicles and the highest percentages of large size follicles were seen in LPA+/LPA- group (p
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- 2021
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29. Effect of Lysophosphatidic Acid on the Vascular Endothelial Growth Factor Expression in Autotransplanted Mouse Ovaries Encapsulated in Sodium Alginate.
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Dehghan, Maryam, Shahbazi, Shirin, and Salehnia, Mojdeh
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- *
VASCULAR endothelial growth factors , *LYSOPHOSPHOLIPIDS , *OVARIES , *CORPUS luteum , *OVARIAN reserve , *ALGINATES , *SODIUM alginate - Abstract
Objective: The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) supplementation during in vitro culture and transplantation of mouse ovaries on the follicular development and expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor at the mRNA and protein levels. Materials and methods: Three weeks old mice ovaries were cultured in the presence and absence of LPA for 24 hours, then they were capsulated in sodium alginate in the presence and absence of LPA as four experimental groups. After transplantation the vaginal smears were performed daily to evaluate the initiation of the estrous cycle. The morphology and follicular distribution were analyzed at the first and fourth estrous cycles using hematoxylin and eosin staining. Then in the groups that showed higher and lower follicular development the immunohistochemistry assay was conducted to identify VEGF protein expression, and the real time RT-PCR was done to analyze the expression of Vegf gene at the first estrus cycle. Results: The large size follicles and also the corpus luteum were prominent in all transplanted groups at fourth estrus cycle in comparison with intact control groups. The statistically lowest percentage of small size follicles and the highest percentages of large size follicles were seen in LPA+/LPA- group (p<0.05). The expression ratio of Vegf to β-actin was significantly higher in this group in comparison with non-LPA treated and intact control groups (p <0.05). Conclusion: LPA as an angiogenesis factor increases the follicular development in transplanted ovaries but it causes early discharge of ovarian reserve. [ABSTRACT FROM AUTHOR]
- Published
- 2021
30. Skeletal myofiber VEGF is essential for the exercise training response in adult mice
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Delavar, Hamid, Nogueira, Leonardo, Wagner, Peter D, Hogan, Michael C, Metzger, Daniel, and Breen, Ellen C
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Medical Physiology ,Biomedical and Clinical Sciences ,Health Sciences ,Sports Science and Exercise ,Cardiovascular ,Prevention ,Underpinning research ,1.1 Normal biological development and functioning ,Aging ,Angiogenesis Inducing Agents ,Animals ,Capillaries ,Mice ,Mice ,Knockout ,Muscle Fibers ,Skeletal ,Oxygen ,Physical Conditioning ,Animal ,Running ,Vascular Endothelial Growth Factor A ,angiogenesis ,exercise ,metabolism ,peripheral vascular disease ,Biological Sciences ,Medical and Health Sciences ,Physiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Vascular endothelial growth factor (VEGF) is exercise responsive, pro-angiogenic, and expressed in several muscle cell types. We hypothesized that in adult mice, VEGF generated within skeletal myofibers (and not other cells within muscle) is necessary for the angiogenic response to exercise training. This was tested in adult conditional, skeletal myofiber-specific VEGF gene-deleted mice (skmVEGF-/-), with VEGF levels reduced by >80%. After 8 wk of daily treadmill training, speed and endurance were unaltered in skmVEGF-/- mice, but increased by 18% and 99% (P < 0.01), respectively, in controls trained at identical absolute speed, incline, and duration. In vitro, isolated soleus and extensor digitorum longus contractile function was not impaired in skmVEGF-/- mice. However, training-induced angiogenesis was inhibited in plantaris (wild type, 38%, skmVEGF-/- 18%, P < 0.01), and gastrocnemius (wild type, 43%, P < 0.01; skmVEGF-/-, 7%, not significant). Capillarity was maintained (different from VEGF gene deletion targeted to multiple cell types) in untrained skmVEGF-/- mice. Arteriogenesis (smooth muscle actin+, artery number, and diameter) and remodeling [vimentin+, 5'-bromodeoxycytidine (BrdU)+, and F4/80+ cells] occurred in skmVEGF-/- mice, even in the absence of training. skmVEGF-/- mice also displayed a limited oxidative enzyme [citrate synthase and β-hydroxyacyl CoA dehydrogenase (β-HAD)] training response; β-HAD activity levels were elevated in the untrained state. These data suggest that myofiber expressed VEGF is necessary for training responses in capillarity and oxidative capacity and for improved running speed and endurance.
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- 2014
31. De Novo Cerebrovascular Malformation in the Adult Mouse After Endothelial Alk1 Deletion and Angiogenic Stimulation
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Chen, Wanqiu, Sun, Zhengda, Han, Zhenying, Jun, Kristine, Camus, Marine, Wankhede, Mamta, Mao, Lei, Arnold, Tom, Young, William L, and Su, Hua
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Pediatric ,Congenital Structural Anomalies ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Activin Receptors ,Type I ,Activin Receptors ,Type II ,Adenoviridae ,Angiogenesis Inducing Agents ,Animals ,Antimetabolites ,Antineoplastic Agents ,Hormonal ,Bromodeoxyuridine ,Cell Proliferation ,Central Nervous System Vascular Malformations ,Endothelial Cells ,Exons ,Gene Deletion ,Mice ,Organisms ,Genetically Modified ,Tamoxifen ,Telangiectasia ,Hereditary Hemorrhagic ,Vascular Endothelial Growth Factor A ,AVM (arteriovenous malformation) intracranial ,models ,animal ,telangiectasia ,hereditary hemorrhagic ,type 2 ,models ,animal ,telangiectasia ,hereditary hemorrhagic ,type 2 ,Cardiorespiratory Medicine and Haematology ,Neurology & Neurosurgery ,Clinical sciences ,Allied health and rehabilitation science - Abstract
Background and purposeIn humans, activin receptor-like kinase 1 (Alk1) deficiency causes arteriovenous malformations (AVMs) in multiple organs, including the brain. Focal Alk1 pan-cellular deletion plus vascular endothelial growth factor stimulation induces brain AVMs in the adult mouse. We hypothesized that deletion of Alk1 in endothelial cell (EC) alone plus focal vascular endothelial growth factor stimulation is sufficient to induce brain AVM in the adult mouse.MethodsFocal angiogenesis was induced in the brain of 8-week-old Pdgfb-iCreER;Alk1(2f/2f) mice by injection of adeno-associated viral vectors expressing vascular endothelial growth factor. Two weeks later, EC-Alk1 deletion was induced by tamoxifen treatment. Vascular morphology was analyzed, and EC proliferation and dysplasia index (number of vessels with diameter>15 μm per 200 vessels) were quantified 10 days after tamoxifen administration.ResultsTangles of enlarged vessels resembling AVMs were present in the brain angiogenic region of tamoxifen-treated Pdgfb-iCreER;Alk1(2f/2f) mice. Induced brain AVMs were marked by increased dysplasia index (P
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- 2014
32. Genetic markers for preeclampsia in Peruvian women.
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Pacheco-Romero, José, Acosta Conchucos, Oscar, Huerta Canales, Doris, Cabrera Ramos, Santiago, Vargas Chávez, Marlene, Mascaro Sánchez, Pedro, Huamán Guerrero, Moisés, Sandoval Paredes, José, López Gabriel, Rudy, Mateus, Julio, Gil Guevara, Enrique, Guevara Rios, Enrique, Butrica Ferré, Nitza, Catari Soto, Diana, Bellido Yarlequé, David, Custodio González, Gina, and Naranjo Adonaire, Andrea
- Subjects
- *
DNA analysis , *INTERLEUKINS , *GENETIC polymorphisms , *ALLELES , *PREECLAMPSIA , *GENETIC markers , *GENES , *GENOTYPES , *APOLIPOPROTEINS , *VASCULAR endothelial growth factors , *POLYMERASE chain reaction , *WOMEN'S health - Abstract
Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbimortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele. [ABSTRACT FROM AUTHOR]
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- 2021
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33. Fibroblasts derived from human pluripotent stem cells activate angiogenic responses in vitro and in vivo.
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Shamis, Yulia, Silva, Eduardo A, Hewitt, Kyle J, Brudno, Yevgeny, Levenberg, Shulamit, Mooney, David J, and Garlick, Jonathan A
- Subjects
Extremities ,Pericytes ,Fibroblasts ,Endothelial Cells ,Pluripotent Stem Cells ,Animals ,Humans ,Mice ,Ischemia ,Proteome ,Angiogenesis Inducing Agents ,Stem Cell Transplantation ,Cell Differentiation ,Neovascularization ,Physiologic ,Embryonic Stem Cells ,Induced Pluripotent Stem Cells ,Biomarkers ,Neovascularization ,Physiologic ,General Science & Technology - Abstract
Human embryonic and induced pluripotent stem cells (hESC/hiPSC) are promising cell sources for the derivation of large numbers of specific cell types for tissue engineering and cell therapy applications. We have describe a directed differentiation protocol that generates fibroblasts from both hESC and hiPSC (EDK/iPDK) that support the repair and regeneration of epithelial tissue in engineered, 3D skin equivalents. In the current study, we analyzed the secretory profiles of EDK and iPDK cells to investigate the production of factors that activate and promote angiogenesis. Analysis of in vitro secretion profiles from EDK and iPDK cells demonstrated the elevated secretion of pro-angiogenic soluble mediators, including VEGF, HGF, IL-8, PDGF-AA, and Ang-1, that stimulated endothelial cell sprouting in a 3D model of angiogenesis in vitro. Phenotypic analysis of EDK and iPDK cells during the course of differentiation from hESCs and iPSCs revealed that both cell types progressively acquired pericyte lineage markers NG2, PDGFRβ, CD105, and CD73 and demonstrated transient induction of pericyte progenitor markers CD31, CD34, and Flk1/VEGFR2. Furthermore, when co-cultured with endothelial cells in 3D fibrin-based constructs, EDK and iPDK cells promoted self-assembly of vascular networks and vascular basement membrane deposition. Finally, transplantation of EDK cells into mice with hindlimb ischemia significantly reduced tissue necrosis and improved blood perfusion, demonstrating the potential of these cells to stimulate angiogenic responses in vivo. These findings demonstrate that stable populations of pericyte-like angiogenic cells can be generated with high efficiency from hESC and hiPSC using a directed differentiation approach. This provides new cell sources and opportunities for vascular tissue engineering and for the development of novel strategies in regenerative medicine.
- Published
- 2013
34. Self-assembled and dynamic bond crosslinked herb-polysaccharide hydrogel with anti-inflammation and pro-angiogenesis effects for burn wound healing.
- Author
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Wu H, Wang T, Liang Y, Chen L, and Li Z
- Subjects
- Animals, Rats, Angiogenesis Inducing Agents, Anti-Inflammatory Agents pharmacology, Polysaccharides, Wound Healing, Anti-Bacterial Agents, Hydrogels, Burns drug therapy
- Abstract
Excessive inflammation and defective angiogenesis can affect burn wound healing. Recently, naturally derived substances with anti-inflammatory and proangiogenic properties have attracted public attention. The design and fabrication of naturally derived substance-based bioactive hydrogels as wound dressings are of interest and important for regulating the complex microenvironment of the wound bed. Herein, we developed a hydrogel by self-assembling a natural herb (glycyrrhizic acid, GA) dynamic Schiff base crosslinking of hyaluronic acid derivatives and integrating deferoxamine (DFO). The naturally derived herbal GA endowed the bioactive hydrogel with a native anti-inflammatory capability. The introduction of dynamic bond crosslinking improved the hydrogel stability. In addition, dynamic crosslinking is conducive for integrating the naturally-derived DFO, delivering it to the wound site, and promoting angiogenesis. Rheological tests, injectability, degradation behavior, and drug release performance demonstrated the enhanced stability of the hydrogel and sustained release of DFO. Cytotoxicity, cell proliferation, and cell migration tests suggested that the hydrogel was biocompatible. Further, the hydrogel exerted anti-inflammatory and angiogenic effects and accelerated burn wound healing in rats. Therefore, the proposed hydrogel has the potential to be a natural, herb-based, bioactive dressing for burn wound management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
- Full Text
- View/download PDF
35. Structural determination and pro-angiogenic effect of polysaccharide from the pollen of Typha angustifolia L
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Mingliang, Gao, Jinshan, Lan, Yuling, Zha, Weifeng, Yao, Beihua, Bao, Mingqiu, Shan, Fang, Zhang, Guisheng, Zhou, Sheng, Yu, Fangfang, Cheng, Yudan, Cao, Hui, Yan, Li, Zhang, and Peidong, Chen
- Subjects
Phosphatidylinositol 3-Kinases ,Polysaccharides ,Structural Biology ,Monosaccharides ,Animals ,Pollen ,Angiogenesis Inducing Agents ,General Medicine ,Typhaceae ,Molecular Biology ,Biochemistry ,Zebrafish - Abstract
Four fractions of polysaccharides (TPP-1, TPP-2, TPP-3, and TPP-4) were isolated and purified from the pollen of Typha angustifolia L., and the structure of TPP-3 was furtherly determined by HPGPC (High Performance Gel Permeation Chromatography), monosaccharide composition analysis, methylation analysis and NMR (Nuclear Magnetic Resonance). TPP-3 was found to be a homogeneous heteropolysaccharide with an average molecular weight of 5.5 × 10
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- 2022
36. Vocal fold fibroblasts promote angiogenesis in vocal fold leukoplakia by secreting pro-angiogenic factors
- Author
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Yinying Chu, Yi Fang, Haitao Wu, Jian Chen, and Lei Cheng
- Subjects
Vascular Endothelial Growth Factor A ,Neovascularization, Pathologic ,Otorhinolaryngology ,Endothelial Cells ,Humans ,Vimentin ,Angiogenesis Inducing Agents ,Surgery ,Vocal Cords ,General Medicine ,Fibroblasts ,Laryngeal Neoplasms ,Leukoplakia - Abstract
Cancer-associated fibroblasts (CAFs) have been reported to play an essential role in tumor angiogenesis and progression. In this study, we aimed to investigate the impact of vocal fold leukoplakia-associated fibroblasts (VFLFs) on the angiogenesis process in vocal fold leukoplakia (VFL) and their potential secretions of proangiogenic factors.A total of 160 lesions (86 laryngeal carcinoma, 67 vocal fold leukoplakia, 7 vocal fold polyp) were detected under narrow band imaging (NBI) mode to evaluate the relationship between pathology and intraepithelial papillary capillary loop (IPCL) grades. We characterized immortalized vocal fold CAFs, VFLFs, normal fibroblasts (NFs) cell lines using immunofluorescence cytochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). The effects of fibroblast conditioned media (CM) on the proliferative, migrating and tube formation capacity of human umbilical vein endothelial cells (HUVEC) were investigated using the cell counting kit-8 (CCK-8) assay, wound healing assay, transwell migration experiment and Matrigel tube formation experiment. The expression levels of proangiogenic factors in CAFs, VFLFs, and NFs were evaluated by antibody microarray and RT-qPCR.NBI images depicted that angiogenesis was abnormally activated during laryngeal tumorigenesis. Both CAF and VFLF expressed Vimentin, alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). NF expressed Vimentin and α-SMA, but not FAP. The PCR results showed that mRNA expression levels of Vimentin, α-SMA and FAP in CAFs and VFLFs were significantly increased than those in NFs. CAF-CM and VFLF-CM promoted the proliferative, migrating, and tube formation ability of HUVECs. Secretome profiling of fibroblasts by antibody microarray demonstrated that VFLFs secreted significantly more vascular endothelial growth factor (VEGF), angiogenin, bFGF and HGF than NFs.Overall, we demonstrated that VEGF, angiogenin, bFGF and HGF derived from VFLFs may play crucial roles in the angiogenesis process of laryngeal premalignant and malignant lesions. This may contribute to the exploitation of novel therapeutic strategies for VFL.
- Published
- 2022
37. Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre‐eclampsia
- Author
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Alan Wright, Peter von Dadelszen, Laura A. Magee, Argyro Syngelaki, Ranjit Akolekar, Dave Wright, and Kypros H. Nicolaides
- Subjects
Vascular Endothelial Growth Factor Receptor-1 ,Pre-Eclampsia ,Pregnancy ,Predictive Value of Tests ,Pregnancy Trimester, Third ,Humans ,Obstetrics and Gynecology ,Female ,Angiogenesis Inducing Agents ,Gestational Age ,Biomarkers ,Placenta Growth Factor - Abstract
To examine the effect of self-declared race on serum placental growth factor (PlGF) and sFlt-1/PlGF ratio and the impact on pre-eclampsia (PE) prediction.Prospective observational study.Two UK maternity hospitals.29 035 women with singleton pregnancies attending a routine 35The predictive performance of PlGF and sFlt-1/PlGF for PE in minority racial groups (versus white) was examined.Delivery with PE.Compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut-off corresponding to a screen-positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut-off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut-off in sFlt-1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient-specific risks.Screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.
- Published
- 2022
38. Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers
- Author
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Blume, Peter, Driver, Vickie R, Tallis, Arthur J, Kirsner, Robert S, Kroeker, Roy, Payne, Wyatt G, Wali, Soma, Marston, William, Dove, Cyaandi, Engler, Robert L, Chandler, Lois A, and Sosnowski, Barbara K
- Subjects
Peripheral Neuropathy ,Neurodegenerative ,Diabetes ,Neurosciences ,Adenoviridae ,Angiogenesis Inducing Agents ,Becaplermin ,Collagen ,Diabetic Foot ,Gels ,Genetic Therapy ,Genetic Vectors ,Humans ,Platelet-Derived Growth Factor ,Proto-Oncogene Proteins c-sis ,Wound Healing ,Clinical Sciences ,Dermatology & Venereal Diseases - Abstract
We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5-10.0 cm(2) chronic diabetic neuropathic foot ulcers that healed
- Published
- 2011
39. Vaccarin hastens wound healing by promoting angiogenesis via activation of MAPK/ERK and PI3K/AKT signaling pathways in vivo
- Author
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Bao Hou, Weiwei Cai, Ting Chen, Zhixuan Zhang, Haifeng Gong, Wei Yang, and Liying Qiu
- Subjects
Vaccaria ,Angiogenesis Inducing Agents ,Wound Healing ,Rats ,Surgery ,RD1-811 - Abstract
Abstract Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats’ skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.
- Published
- 2020
- Full Text
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40. Effect of a novel bioceramic root canal sealer on the angiogenesis-enhancing potential of assorted human odontogenic stem cells compared with principal tricalcium silicate-based cements
- Author
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Keziban Olcay, Pakize Neslihan Taşli, Esra Pamukçu Güven, Gül Merve Yalçın Ülker, Emine Esen Öğüt, Elif Çiftçioğlu, Binnur Kiratli, and Fikrettin Şahin
- Subjects
Angiogenesis inducing agents ,Dental cements ,Regenerative endodontics ,Stem cells ,Dentistry ,RK1-715 - Abstract
Abstract Objective: This study evaluated the angiogenesis-enhancing potential of a tricalcium silicate-based mineral trioxide aggregate (ProRoot MTA), Biodentine, and a novel bioceramic root canal sealer (Well-Root ST) in human dental pulp stem cells (hDPSCs), human periodontal ligament stem cells (hPLSCs), and human tooth germ stem cells (hTGSCs). Methodology: Dulbecco's modified Eagle's medium was conditioned for 24 h by exposure to ProRoot MTA, Biodentine, or Well-Root ST specimens (prepared according to the manufacturers’ instructions). The cells were cultured in these conditioned media and their viability was assessed with 3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H tetrazolium (MTS) on days 1, 3, 7, 10, and 14. Angiogenic growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF-2), and vascular endothelial growth factor (VEGF)] were assayed by sandwich enzyme-linked immunosorbent assay (ELISA) on days 1, 7, and 14. Human umbilical vein endothelial cell (HUVEC) migration assays were used to evaluate the vascular effects of the tested materials at 6–8 h. Statistical analyses included Kruskal–Wallis, Mann–Whitney U, and Friedman and Wilcoxon signed rank tests. Results: None of tricalcium silicate-based materials were cytotoxic and all induced a similar release of angiogenic growth factors (PDGF, FGF-2, and VEGF) (p>0.05). The best cell viability was observed for hDPSCs (p
- Published
- 2020
- Full Text
- View/download PDF
41. The effects of proteins released from silk mat layers on macrophages
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Ju-Won Kim, You-Young Jo, Hae Yong Kweon, Dae-Won Kim, and Seong-Gon Kim
- Subjects
Silk ,Inflammation ,Angiogenesis inducing agents ,Dentistry ,RK1-715 ,Surgery ,RD1-811 - Abstract
Abstract Background The objective of this study was to evaluate the changes in gene expression after incubation of cells with proteins released from different silk mat layers. Methods A silk cocoon from Bombyx mori was separated into four layers of equal thickness. The layers were numbered from 1 to 4 (from the inner to the outer layer). The proteins were released by sonication of a silk mat layer in normal saline. The concentration of proteins was determined by spectrophotometry. They were incubated with RAW264.7 cells, and changes in the expression of genes were evaluated by cDNA microarray analysis and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results Layer 1 and 4 groups had higher protein concentrations compared to those in layer 2 and 3 groups. The genes associated with inflammation and angiogenesis showed significantly higher expression in layer 1 and 4 groups. The results of qRT-PCR were in agreement with those of the cDNA microarray analysis. Conclusions The silk mat from the middle portion of the silkworm cocoon yielded a lower protein release and caused an insignificant change in the expression of genes that are associated with inflammation and angiogenesis.
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- 2018
- Full Text
- View/download PDF
42. Angiogenesis in cutaneous disease: Part I
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Nguyen, Amy, Hoang, Van, Laquer, Vivian, and Kelly, Kristen M
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Angiogenesis Inducing Agents ,Angiogenesis Inhibitors ,Animals ,Humans ,Neovascularization ,Pathologic ,Neovascularization ,Physiologic ,Skin Diseases ,angiogenesis ,antiangiogenic agents ,dermatology ,Dermatology & Venereal Diseases ,Clinical sciences - Abstract
UnlabelledAngiogenesis is an important process in normal physiology and disease pathogenesis. Angiogenesis is controlled in a healthy body by a system of angiogenic growth factors and angiogenesis inhibitors. When angiogenic growth factors are predominantly expressed, blood vessel growth occurs and disease may result. Successful therapies have been developed that target growth factors, their receptors, or the cascade pathways that are activated by growth factor/receptor interactions. There is good evidence that angiogenesis plays an important role in a wide range of cutaneous maladies, and angiogenesis-targeting therapies are playing an increasing role in the management of dermatologic disease. Cutaneous angiogenesis offers an exciting new arena for targeted dermatologic therapeutics.Learning objectivesAfter completing this learning activity, participants should be able to distinguish angiogenic growth factors and inhibitors, recognize angiogenic mediating agents and compare their mechanisms of action, and apply the use of angiogenic mediating agents in clinical and research situations.
- Published
- 2009
43. Angiogenesis in cutaneous disease: Part II
- Author
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Laquer, Vivian, Hoang, Van, Nguyen, Amy, and Kelly, Kristen M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Regenerative Medicine ,Angiogenesis Inducing Agents ,Humans ,Neovascularization ,Pathologic ,Skin Diseases ,Skin Neoplasms ,Vascular Malformations ,angiogenesis ,antiangiogenic agents ,dermatology ,Clinical Sciences ,Dermatology & Venereal Diseases ,Clinical sciences - Abstract
UnlabelledThis review will discuss the role of angiogenesis in specific cutaneous diseases. Scientific evidence now points to the role of angiogenesis in tumor development and many other cutaneous disorders. Angiogenesis is a complex process that involves angiogenic growth factors and inhibitors, many of which could be a potential target for pharmacologic intervention. Antiangiogenic agents have recently been applied to dermatologic diseases with promising efficacy.Learning objectivesAfter completing this learning activity, participants should be able to recognize cutaneous diseases where angiogenesis is likely to be an important factor, recognize scenarios where angiogenic therapy may be useful in conjunction with traditional therapies, and be able to use angiogenic-mediating agents in the treatment of dermatologic disease.
- Published
- 2009
44. Association of fetal sex with angiogenic factors in normotensive and hypertensive pregnancy states
- Author
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Gabriel A, Arenas, Nikolina, Docheva, Joana, Lopes Perdigao, Ariel, Mueller, Tinyan, Dada, and Sarosh, Rana
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Vascular Endothelial Growth Factor Receptor-1 ,Obstetrics and Gynecology ,Pre-Eclampsia ,Pregnancy ,Hypertension ,Internal Medicine ,Humans ,Angiogenesis Inducing Agents ,Female ,Biomarkers ,Placenta Growth Factor ,Retrospective Studies - Abstract
With the incorporation of angiogenic biomarkers into clinical practice, identification of potential modifiers of the angiogenic profile, including fetal sex, is essential.In this retrospective cohort analysis, patients with hypertensive disorders of pregnancy (HDP) and normotensive pregnancies were enrolled upon admission to Labor and Delivery. Blood samples for angiogenic factors were assessed using an automated platform. Clinical and demographic information was abstracted from each patient's medical records.Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) levels and their ratio in relation to fetal sex in patients with normotensive pregnancies compared to those with HDP were evaluated.A total of 617 patients were analyzed (299 normotensive, 113 gestational hypertensive, 71 chronic hypertensive, and 134 preeclamptic patients). There was no difference between the number of patients who had a male fetus among preeclampsia and normotensive parturients (56.0 % vs 50.2 %, p = 0.26). Normotensive patients carrying a male fetus had significantly higher sFlt1 (pg/ml) (3168 [IQR: 2160-4945] vs 2678 [IQR: 1752-4271]; p = 0.01) and sFlt1/PlGF ratios (18 [IQR: 7-44] vs 12 [IQR: 5-30]; p = 0.01) in comparison to pregnant patients carrying a female fetus. This difference between fetal sexes was not observed in the angiogenic profile of patients with HDP.Our study of primarily Black, obese patients demonstrates that normotensive patients carrying a male fetus have a significantly higher sFlt1 and sFlt1/PlGF ratio as compared to those carrying a female fetus at term gestation. Fetal sex should be considered as a covariate when studying angiogenic factors in normotensive pregnant patients.
- Published
- 2022
45. Morphogenesis of vascular and neuronal networks and the relationships between their remodeling processes
- Author
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Ribatti, Domenico and Guidolin, Diego
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NGF ,Neurons ,Vascular Endothelial Growth Factor A ,General Neuroscience ,Morphogenesis ,Morphogenesis: neurogenesis ,Angiogenesis Inducing Agents ,Angiogenesis ,VEGF ,Axons - Abstract
Vascular and neuronal networks represent important examples of body structures created by processes of branching morphogenesis. Migration to an appropriate target in both axons and blood vessels are mediated by chemo-repulsive and attractive signals and the proximity of nerves and blood vessels suggest that there may be a molecular crosstalk and common cues between nerves and blood vessels. Vascular endothelial growth factor (VEGF), a key angiogenetic factor, has direct effects on the nervous system in terms of axon outgrowth and survival. Conversely, nerve growth factor (NGF), a well-known neurotropic molecule, exhibits angiogenic properties. Available data on the morphogenesis of vascular and neuronal networks and on the relationships between their remodeling processes will be the focus of the present study.
- Published
- 2022
46. N4BP3 promotes angiogenesis in hepatocellular carcinoma by binding with KAT2B
- Author
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Hexu Han, Wei Zhu, Ting Lin, Cuixia Liu, and Hengyong Zhai
- Subjects
STAT3 Transcription Factor ,Cancer Research ,Carcinoma, Hepatocellular ,Neovascularization, Pathologic ,Liver Neoplasms ,Mice, Nude ,General Medicine ,Lysine Acetyltransferases ,Sorafenib ,Histones ,Oxygen ,Mice ,Oncology ,Cell Line, Tumor ,Animals ,Humans ,Angiogenesis Inducing Agents ,Cell Proliferation - Abstract
Although angiogenesis is a critical event in hepatocellular carcinoma (HCC), and this process provides the tumor with sufficient oxygen and nutrients, the precise molecular mechanism by which it occurs is not fully understood. NEDD4 binding protein 3 (N4BP3) was identified in this study as a novel pro-angiogenic factor in HCC cell lines and tissues. We discovered that N4BP3 was significantly expressed in HCC and that its level of expression was positively correlated with the density of tumor microvessels in HCC tissues. Cell biology experiments have shown that N4BP3 knockdown in HCC cells significantly inhibits the formation of complete tubular structures by HUVECs in vitro and HCC angiogenesis in vivo. In HCC cells, overexpression of N4BP3 has the opposite effects. Further cell and molecular biology experiments have revealed that N4BP3 interacts with KAT2B (lysine acetyltransferase 2B), increasing signal transducer and activator of transcription 3 (STAT3) expression by regulating the distribution of acetyl-histone H3 (Lys27) (H3K27ac) in its promoter region. This, in addition, regulates the activity of the STAT3 signaling pathway, which promotes the proliferation of microvessels in HCC and accelerates the malignant process of the tumor. In vivo experiments in nude mice have confirmed our findings, and also suggested that N4BP3 could be a potential target for the treatment of HCC in combination with sorafenib.
- Published
- 2022
47. An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry
- Author
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Nerolen Soobryan, Ajit Kumar, Jagidesa Moodley, and Irene Mackraj
- Subjects
Vascular Endothelial Growth Factor A ,Vascular Endothelial Growth Factor Receptor-1 ,Infant, Newborn ,Obstetrics and Gynecology ,Hypertension, Pregnancy-Induced ,Transforming Growth Factor beta1 ,Cohort Studies ,Pre-Eclampsia ,Pregnancy ,Humans ,Pregnancy-Associated Plasma Protein-A ,Female ,Angiogenesis Inducing Agents ,Biomarkers - Abstract
Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (
- Published
- 2022
48. Cohort study on the differential expression of inflammatory and angiogenic factors in thrombi, cerebral and peripheral plasma following acute large vessel occlusion stroke
- Author
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Xavier O Scott, Stephanie H Chen, Roey Hadad, Dileep Yavagal, Eric C Peterson, Robert M Starke, W Dalton Dietrich, Robert W Keane, and Juan Pablo de Rivero Vaccari
- Subjects
Vascular Endothelial Growth Factor A ,Vascular Endothelial Growth Factor C ,Vascular Endothelial Growth Factor D ,Cohort Studies ,Humans ,Lymphotoxin-alpha ,Ischemic Stroke ,Placenta Growth Factor ,Interleukin-15 ,Interleukin-16 ,Interleukin-13 ,Interleukin-6 ,Interleukin-17 ,Interleukin-8 ,Granulocyte-Macrophage Colony-Stimulating Factor ,Original Articles ,Interleukin-12 ,Stroke ,Neurology ,Cytokines ,Interleukin-2 ,Angiogenesis Inducing Agents ,Female ,Neurology (clinical) ,Interleukin-4 ,Interleukin-5 ,Cardiology and Cardiovascular Medicine ,Biomarkers - Abstract
Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1β, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-β, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.
- Published
- 2023
49. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue
- Author
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Feugate, JE, Wong, L, Li, QJ, and Martins-Green, M
- Subjects
chemokine ,ECM ,tenascin ,fibronectin ,collagen ,wound healing ,Angiogenesis Inducing Agents ,Animals ,Avian Proteins ,Cell Movement ,Cells ,Cultured ,Chemokines ,CXC ,Chick Embryo ,Collagen Type I ,Collagen Type II ,Cytokines ,Extracellular Matrix Proteins ,Fibroblasts ,Fibronectins ,Granulation Tissue ,Humans ,Interleukin-8 ,Muscle ,Smooth ,Vascular ,Peptides ,Sequence Homology ,Amino Acid ,Tenascin ,Wound Healing ,Biochemistry and Cell Biology ,Biochemistry & Molecular Biology - Abstract
Background: During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF), is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM) is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results: Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions: These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds. © 2002 Feugate et al; licensee BioMed Central Ltd.
- Published
- 2002
50. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue
- Author
-
Feugate, Jo Ellen, Wong, Lina, Li, Qi-Jing, and Martins-Green, Manuela
- Subjects
Angiogenesis Inducing Agents ,Animals ,Avian Proteins ,Cell Movement ,Cells ,Cultured ,Chemokines ,CXC ,Chick Embryo ,Collagen Type I ,Collagen Type II ,Cytokines ,Extracellular Matrix Proteins ,Fibroblasts ,Fibronectins ,Granulation Tissue ,Humans ,Interleukin-8 ,Muscle ,Smooth ,Vascular ,Peptides ,Sequence Homology ,Amino Acid ,Tenascin ,Wound Healing ,chemokine ,ECM ,tenascin ,fibronectin ,collagen ,wound healing - Abstract
Background: During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF), is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM) is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results: Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions: These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds. © 2002 Feugate et al; licensee BioMed Central Ltd.
- Published
- 2002
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