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Objective: The aim of this study was to observe the surgical wound healing process in patients with multiple myeloma who had undergone surgery. Method: We collected clinical data on patients with multiple myeloma and observed wound healing following surgical therapy. Additionally, we compared the expression of angiogenesis markers in patients with and without multiple myeloma (undergoing surgical excision of other tumour tissues). In patients who had multiple myeloma bone disease, we examined several clinical features: haemoglobin levels; albumin levels; blood glucose levels; and surgery programme. We then compared expression levels of the angiogenesis markers CD31, CD34 and vascular endothelial growth factor (VEGF) in samples scraped from the skin margin of the surgical incision in 12 patients without multiple myeloma (control) and nine patients with multiple myeloma. Results: All 61 patients with multiple myeloma observed showed no disunion, no delayed union and no infection in their wound healing. CD31 and VEGF expression was higher in the nine patients with multiple myeloma compared with the 12 control patients without. We observed no difference in CD34 expression between control and experimental groups. Conclusion: The results of this study suggest that patients with multiple myeloma who have undergone surgery recover well and produce higher quantities of new vessels compared with patients without multiple myeloma. This occurs through increased expression of CD31 and VEGF, angiogenic factors which promote wound healing. We did not observe higher expression of these factors contributing to increased incisional implantation metastasis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P

Objective: The purpose of this study was to observe the effect of the accordion technique (AT) during the distraction phase on chondrogenesis and bone regeneration in a rat femoral distraction osteogenesis (DO) model, and investigate its potential mechanism for reducing the total treatment time of DO. Methods: Fifty-four male Sprague-Dawley (SD) rats that were specific-pathogen- free (SPF) were subjected to DO surgery on the right femur. The distraction rate was 0.5mm/day for 10 days, following a latency period of 5 days. Rats were randomly divided into Control (no AT, n = 18), Group LA (low amplitude with AT, n = 18), and Group HA (high amplitude with AT, n = 18) according to different AT protocols in the distraction phase. Rats were respectively euthanized by anesthesia overdose at 2, 4 and 6 weeks of the consolidation phase, and the femurs were harvested. Digital radiography, micro-computed tomography (micro-CT), biomechanical tests, and histomorphological analysis were used to assess the quality of regenerated bone in the distraction area. Results: Digital radiographic, micro-CT, biomechanical tests, and histological analysis revealed an increase in early-stage callus formation (p < 0.05) and improved blood supply to the callus tissue in Group LA, as compared to both the Control and Group HA. The enhanced differentiation of fibrous and cartilaginous tissue into bone tissue was also observed in Group LA, leading to improved strength and stiffness (p < 0.05) of the regenerated bone at 6 weeks of the consolidation phase. The angiogenic (hypoxia-inducible factor--1α (HIF--1α) and vascular endothelial growth factor (VEGF), p < 0.05) and osteogenic (runt- related transcription factor 2 (RUNX2), osteocalcin (OCN) and osteopontin (OPN), p < 0.05) biomarkers were higher expressed in Group LA at 2 and 4 weeks of consolidation phase, whereas decreased at 6 weeks of consolidation phase. Conclusion: The application of ATwith lowamplitude during the distraction phase can enhance chondrogenesis and bone regeneration by activating the angiogenesis factor pathway and upregulating the expression of osteogenic-related biomarkers such as HIF-1α, VEGF, RUNX2, OCN, and OPN. [ABSTRACT FROM AUTHOR]

Background and objective: The aims of this study were to create Bisphonates Related Osteonecrosis of the Jaw (BRONJ) in rats and treat them with an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts). Materials and methods: Thirty female Wistar rats were procured. Rats were labeled as Group I to III. Group I = Osteoblast group, Group II = A-Heal and Group III Control group. In Groups I-III, BRONJ was created and treated in Group I with ABMDO, Group II with A-Heal and Group III was the control group. At the end of the four weeks post treatment, all the animals were humanely killed. The intact maxillae were removed in total. Histopathological and radiological examinations were carried out with physicians blinded to the groups. Results: Computerized tomography revealed that Groups I and II demonstrated the presence of dense osteosclerosis, intralesional calcifications, and adequate healing of the overlying soft tissues compared to Group III, which showed the presence of bone erosions at the alveolar ridge with a lack of intralesional calcifications and ulceration of the overlying soft tissues. Histologically, H&E staining Group 1 and Group 2 both showed marked reactive bone formation. Group 2 additionally revealed the most prominent vascular proliferation (also highlighted by Factor VIII, an endothelial cell marker) among all groups. Group 3 showed cartilaginous proliferation with less reactive bone formation, implicating decreased endochondral ossification compared to Groups 1 and 2. Conclusion: This study shows that angiogenesis factor (A-Heal) and ABMDO were successful in the treatment of experimentally created BRONJ in an animal model.

The aims of this study were to create Bisphonates Related Osteonecrosis of the Jaw (BRONJ) in rats and treat them with an angiogenesis factor (A-Heal) and ABMDO (Autologous Bone Marrow Derived Osteoblasts). Thirty female Wistar rats were procured. Rats were labeled as Group I to III. Group I = Osteoblast group, Group II = A-Heal and Group III Control group. In Groups I-III, BRONJ was created and treated in Group I with ABMDO, Group II with A-Heal and Group III was the control group. At the end of the four weeks post treatment, all the animals were humanely killed. The intact maxillae were removed in total. Histopathological and radiological examinations were carried out with physicians blinded to the groups. Computerized tomography revealed that Groups I and II demonstrated the presence of dense osteosclerosis, intralesional calcifications, and adequate healing of the overlying soft tissues compared to Group III, which showed the presence of bone erosions at the alveolar ridge with a lack of intralesional calcifications and ulceration of the overlying soft tissues. Histologically, H&E staining Group 1 and Group 2 both showed marked reactive bone formation. Group 2 additionally revealed the most prominent vascular proliferation (also highlighted by Factor VIII, an endothelial cell marker) among all groups. Group 3 showed cartilaginous proliferation with less reactive bone formation, implicating decreased endochondral ossification compared to Groups 1 and 2. This study shows that angiogenesis factor (A-Heal) and ABMDO were successful in the treatment of experimentally created BRONJ in an animal model. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (500 mm3 ), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.

Endodontic sealers play a vital role in the obturation of root canal space. The aim of this study was to evaluate the utility of a recently developed polyurethane expandable sealer (PES), along with its cytotoxicity and dimensional changes. L929 fibroblasts and an cell viability assay (MTS assay) were used to determine the cytotoxicity of dental sealers (AH Plus [Dentsply Maillefer, Ballaigues, Switzerland], Sure-Seal Root [Sure Dent Corporation, Gyeonggi-do, South Korea], and the PES) at 24, 48, 72, and 96 hours. An advanced choroidal neovascularization model was used to assess the effect of these sealers on angiogenesis. Thirty-six extracted single-rooted human teeth were prepared and randomly divided into 3 groups (n = 12). Obturation was performed with gutta-percha and a sealer using lateral compaction as follows: group 1, AH Plus; group 2, Sure-Seal; and group 3, PES. The average depth of sealer penetration into dentinal tubules was measured with a scanning electron microscope. Data were analyzed using 1-way analysis of variance and post hoc Tukey tests (level of significance, P <.05). The values of MTS, choroidal neovascularization, and the penetration depth of PES were significantly higher than in other experimental groups (P <.05). The lowest values were noted in specimens of AH Plus, whereas the highest were detected in the PES group. PES showed promising results in terms of biocompatibility and dentinal tubule adaptation and penetration. [ABSTRACT FROM AUTHOR]

Objective: To verify the photobiomodulation effect on angiogenic proteins produced and released by dental human pulpal fibroblasts (HPFs). Material and methods: HPFs were irradiated with 660-nm low-level laser at fluences of 2.5 J/cm2 and 3.7 J/cm2. The control group was not irradiated. MTT, crystal violet, and ELISA assays respectively verified viability, proliferation, and angiogenic protein (supernatant/lysate) at 6 h, 12 h, and 24 h after photobiomodulation. Capillary-like structure formation assay verified functional role. Two-way ANOVA/Tukey's test and ANOVA/Bonferroni's multiple comparisons test respectively verified cell viability/proliferation and intragroup and intergroup comparisons of protein synthesis (p < 0.05). Results: Irradiated and non-irradiated HPFs showed statistically similar cell viability and proliferation pattern. Intragroup comparisons showed similar patterns of protein synthesis for all groups: VEGF-A, VEGF-C, and vascular endothelial growth factor receptor 1 (VEGFR1) increased significantly in the supernatant, while FGF-2 and VEGF-A increased significantly in the lysate. The lower fluence significantly increased BMP-9 (6 h) in the supernatant and VEGFR1 (6 h and 12 h) and VEGF-D (24 h) in the lysate, while the higher fluence significantly increased BMP-9 (6 h) in the supernatant and VEGFR1 (12 h) in the lysate. Regardless of the time, both fluences statistically downregulated placental growth factor (PLGF) and PDGF secretion. Both fluences statistically decreased VEGF-A secretion (24 h) and PLGF production (6 h). Conclusion: Photobiomodulation produced stimulatory effects on angiogenic protein secretion by pulp fibroblasts. In terms of photobiomodulation, over time, both fluences significantly increased the secretion of VEGF-A, VEGF-C, and VEGFR1 and significantly upregulated BMP-9 (6 h) in the supernatant; for capillary-like structure formation, the fluence of 2.5 J/cm2 was better than the fluence of 3.7 J/cm2. Clinical relevance: This study results addressed effective photobiomodulation parameters tailored for pulp angiogenesis. [ABSTRACT FROM AUTHOR]

Objective of this work is to investigate, for the first time, serum concentration of neuropilin-1 (NRP-1), aiming to evaluate its diagnostic performance in endometriosis and usability as a potential non-invasive serum marker of endometriosis. Two hundred women were treated laparoscopically. After laparoscopic surgery women were divided into two groups: 120 women diagnosed with endometriosis and 80 healthy women (control group). Blood samples were taken from all women undergoing laparoscopy half an hour before the induction of anesthesia, for the purpose of collection of serum. The level of NRP-1 in serum was assayed by a standardised sandwich enzyme-linked immunosorbent assay. Differences between endometriosis and healthy control group in NRP-1 levels were significant. All values were significantly and several times higher in patients group, p < .001. After receiver operating characteristic analysis, the area under curve was 0.97 (95% confidence interval: 0.941 to 0.989, p < .0001) at 11 µg/L cut-off level for NRP-1. Preliminary threshold values for NRP-1 in serum were assumed to serve as diagnostic parameters with sensitivity of 99.3% and specificity of 97.8%. Serum concentration of NRP-1 can be considered as a potentially good laboratory diagnostic, non-invasive marker for endometriosis. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm3), intermediate stage (100-300 mm3), advanced stage (300-500 mm3), and end stage (>500 mm3), they were removed by surgery. Then, the expression levels of Hif1a, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC. [ABSTRACT FROM AUTHOR]

Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.

Agents that inhibit angiogenic factors may prevent the development of hepatocellular carcinoma (HCC). Thus, the objective of this study was to kinetically evaluate the antiangiogenic activity of tributyrin (TB), a butyric acid prodrug, in the promotion stage of hepatocarcinogenesis. For this purpose, the resistant hepatocyte (RH) model was used for induction of preneoplastic lesions in Wistar rats. During the promotion phase, the animals received TB or maltodextrin (MD) as control daily. The rats were killed at three time-points (P1, P2 and P3). Increased expression of Vegfa and Vegfr2 was observed during promotion phase of hepatocarcinogenesis, which was not reversed by TB treatment. However, TB treatment reduced the expression of cluster of differentiation (CD) 34-positive vessels at P3 and α-smooth muscle actin (α-SMA)-positive vessels at P2 compared with MD. Enhanced levels of hypoxia inducible factor-1α (HIF-1α) and phosphorylated extracellular signal-regulated kinases (pERK) were detected at P3 when compared with P1 and P2 in the MD treatment. TB treatment reduced the levels of HIF-1α and pERK at P3 relative to the MD control. Experiments with human umbilical vein endothelial cells (HUVEC) showed that sodium butyrate (NaBu) inhibited cell migration and tube formation, confirming the antiangiogenic activity of its prodrug TB. In conclusion, antiangiogenic activity of TB is an early event that already occurs in preneoplastic livers, reinforcing its potential chemopreventive effects against HCC. [ABSTRACT FROM AUTHOR]

Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: “stem cells,” “hypoxic preconditioning,” “ischemic preconditioning,” and “cell transplantation.” Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

Introduction As a tumor grows, the demand for oxygen and nutrients increases and it grows further if acquires the ability to induce angiogenesis. In this study, we aimed to present a two-dimensional continuous mathematical model for avascular tumor growth, coupled with a discrete model of angiogenesis. Materials and Methods In the avascular growth model, tumor is considered as a single mass, which uptakes oxygen through diffusion and invades the extracellular matrix (ECM). After the tumor reaches its maximum size in the avascular growth phase, tumor cells may be in three different states (proliferative, quiescent and apoptotic), depending on oxygen availability. Quiescent cells are assumed to secrete tumor angiogenic factors, which diffuse into the surrounding tissue until reaching endothelial cells. The mathematical model for tumor angiogenesis is consisted of a five-point finite difference scheme to simulate the progression of endothelial cells in ECM and their penetration into the tumor. Results The morphology of produced networks was investigated, based on various ECM degradation patterns. The generated capillary networks involved the rules of microvascular branching and anastomosis. Model predictions were in qualitative agreement with experimental observations and might have implications as a supplementary model to facilitate mathematical analyses for anti-cancer therapies. Conclusion Our numerical simulations could facilitate the qualitative comparison between three layers of tumor cells, their TAF-producing abilities and subsequent penetration of micro-vessels in order to determine the dynamics of microvascular branching and anastomosis in ECM and three different parts of the tumor.

Background: The poor performance of capillary system and reduce in VEGF amount can be mentioned as one of the physiological complications that is caused by aging. Sprint training by more using fibers can be effective in improving performance of older people .The aim of this study was to investigate the effect of eight-week sprint interval training on VEGF amount of soleus muscle tissue and EDL in old Wistar male rats. Methods: A total of twenty aged wistar rats with average weight of 489±43.72 (gr) were prepared and after one week familiarization with the laboratory conditions, were randomly divided into two groups: training (n=10) and control (n=10). SIT Training was included incremental and intermittent running on treadmill that performed threefour times in the week for eight weeks. Then were isolated the soleus and Extensor Digitorum Longus (EDL) muscles. Finally, we used western blot method to measure protein changes in the muscle tissue and t-test evaluating the information. Results: Difference between VEGF amount in control group and training group in both fast-twitch (p≤0.05) and slow-twitch muscles (p≤0.05) was significant. Conclusion: The amount of capillarization in type II fibers have shown more decreases in comparison with type I fibers because of aging, therefor according to the result of this study it can be concluded that sprint interval training may be a proper stimulus to angiogenesis and leads to improvement of its metabolic properties. [ABSTRACT FROM AUTHOR]

Summary: Because diabetic retinopathy increases fracture risk, we studied the association between bone mineral density (BMD) and diabetic retinopathy in a nationally representative sample. A significant association between the presence of diabetic retinopathy and low BMD was observed. Therefore, diabetic retinopathy might be considered as a marker of low BMD. Introduction: Several diabetic complications, including nephropathy, retinopathy, and peripheral neuropathy, are associated with a higher fracture risk in diabetic subjects. However, in contrast to diabetic nephropathy and peripheral neuropathy, which are associated with low bone mineral density (BMD), little is known about the association between BMD and diabetic retinopathy. The aim of the present study was to determine whether the prevalence of diabetic retinopathy is associated with BMD. Methods: This cross-sectional study included a nationally representative sample consisting of 4357 men aged 50 years and older and 4392 postmenopausal women who participated in the Korea National Health and Nutritional Examination Survey (KNHANES) from 2008 to 2011 and underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) and diabetic retinopathy assessments using seven standard gradable photographs. Results: The diabetic women with retinopathy had lower mean BMD at all measured sites than those without retinopathy, although the BMD difference between the two groups was small (3-5 %). In addition, the diabetic women with retinopathy were 2.27 times more likely to have osteoporosis following adjustments for all clinically relevant covariates. However, the prevalence of diabetes mellitus (DM) or diabetic retinopathy was not associated with the prevalence of osteoporosis in men. Conclusions: This study has shown that the presence of diabetic retinopathy is significantly associated with a reduced BMD and increased prevalence of osteoporosis in diabetic women. [ABSTRACT FROM AUTHOR]

The insufficiency of compensatory angiogenesis in the heart of patients with hypertension contributes to heart failure transition. The hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling cascade controls responsive angiogenesis. One of the challenges in reprograming the insufficient angiogenesis is to achieve a sustainable tissue exposure to the proangiogenic factors, such as HIF1α stabilization. In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade. Rnd3 physically interacted with and stabilized HIF1α, and consequently promoted VEGFA expression and endothelial cell tube formation. To demonstrate this proangiogenic role of Rnd3 in vivo, we generated Rnd3 knockout mice. Rnd3 haploinsufficient (Rnd3(+/-)) mice were viable, yet developed dilated cardiomyopathy with heart failure after transverse aortic constriction stress. The poststress Rnd3(+/-) hearts showed significantly impaired angiogenesis and decreased HIF1α and VEGFA expression. The angiogenesis defect and heart failure phenotype were partially rescued by cobalt chloride treatment, a HIF1α stabilizer, confirming a critical role of Rnd3 in stress-responsive angiogenesis. Furthermore, we generated Rnd3 transgenic mice and demonstrated that Rnd3 overexpression in heart had a cardioprotective effect through reserved cardiac function and preserved responsive angiogenesis after pressure overload. Finally, we assessed the expression levels of Rnd3 in the human heart and detected significant downregulation of Rnd3 in patients with end-stage heart failure. We concluded that Rnd3 acted as a novel proangiogenic factor involved in cardiac responsive angiogenesis through HIF1α-VEGFA signaling promotion. Rnd3 downregulation observed in patients with heart failure may explain the insufficient compensatory angiogenesis involved in the transition to heart failure. [ABSTRACT FROM AUTHOR]

The degree of symptomatology of a patient with peripheral arterial disease dictates the kind of treatment. Despite the known therapies, some patients continue to have pain with ambulation, which affects their quality of life. The therapeutic implications of the angiogenic growth factors were identified by the pioneering studies of Folkman et al. 2 decades ago. Further investigations established the possibility of the use of formulations of recombinant angiogenic growth factors, with the objective of developing or increasing the network of collaterals in animal models of chronic myocardial or limb ischemia. Researches suggest that primitive stem cells with whole bone marrow possess greater functional plasticity, capable of contributing to regeneration of ischemic limb muscle and vascular endothelium by adult stem cells. Local autologous marrow stromal cells implantation induces a neovascular response resulting in a significant increase in blood flow to the ischemic limb. In this article we review the studies that have established how the implantation of bone marrow cells into ischemic limbs increases collateral vessel formation.O nível de sintomatologia de um paciente com doença arterial periferal determina o tipo de tratamento. Apesar das terapias conhecidas, alguns pacientes continuam a ter dor com a deambulação, o que afeta sua qualidade de vida. As implicações terapêuticas dos fatores de crescimento angiogênicos foram identificadas por estudos pioneiros de Folkman et al. há 2 décadas. Investigações posteriores estabeleceram a possibilidade de utilizar formulações de fatores de crescimento angiogênico recombinantes, com o objetivo de desenvolver ou aumentar a rede de colaterais em modelos animais de isquemia crônica ou miocárdica. Pesquisas sugerem que células-tronco primitivas com medula óssea possuem maior funcionalidade plástica, capazes de contribuir com a regeneração de músculos isquêmicos e endotélio vascular por células-tronco adultas. O implante local e autólogo de células estromais da medula induz a uma resposta neovascular, resultando em um aumento significativo de fluxo sangüíneo no membro isquêmico. Neste artigo, revisamos os estudos que estabeleceram como o implante de células da medula óssea em membros isquêmicos aumenta a formação de vasos colaterais.

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen "pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer.

Introduction As a tumor grows, the demand for oxygen and nutrients increases and it grows further if acquires the ability to induce angiogenesis. In this study, we aimed to present a two-dimensional continuous mathematical model for avascular tumor growth, coupled with a discrete model of angiogenesis. Materials and Methods In the avascular growth model, tumor is considered as a single mass, which uptakes oxygen through diffusion and invades the extracellular matrix (ECM). After the tumor reaches its maximum size in the avascular growth phase, tumor cells may be in three different states (proliferative, quiescent and apoptotic), depending on oxygen availability. Quiescent cells are assumed to secrete tumor angiogenic factors, which diffuse into the surrounding tissue until reaching endothelial cells. The mathematical model for tumor angiogenesis is consisted of a five-point finite difference scheme to simulate the progression of endothelial cells in ECM and their penetration into the tumor. Results The morphology of produced networks was investigated, based on various ECM degradation patterns. The generated capillary networks involved the rules of microvascular branching and anastomosis. Model predictions were in qualitative agreement with experimental observations and might have implications as a supplementary model to facilitate mathematical analyses for anti-cancer therapies. Conclusion Our numerical simulations could facilitate the qualitative comparison between three layers of tumor cells, their TAF-producing abilities and subsequent penetration of micro-vessels in order to determine the dynamics of microvascular branching and anastomosis in ECM and three different parts of the tumor. [ABSTRACT FROM AUTHOR]

Se estudió el efecto angiogénico y la composición de proteínas y lípidos del omentum humano a partir de la inoculación intraestromal en la córnea de conejo de los extractos obtenidos tras homogeneizar el material biológico. Se encontraron valores muy bajos de proteínas y muy elevados de triglicéridos fundamentalmente en el extracto 2 de origen lipídico. En relación con la vascularización, ésta se logró con mayor intensidad en la córnea de los animales que se inocularon con el extracto 2.It was studied the angiogenic effect and the composition of proteins and lipids of the human omemtum by the intrastromal inoculation into the rabbit's cornea of the extracts obtained after homogenizing the biological material. Extremely low values of proteins and very high values of triglycerides were found mainly in the extract 2 of lipidic origin. Regarding vascularization, it was attained with greater intensity in the cornea of those animals that were inoculated the extract 2.

Objective To investigate the effects of traditional Chinese medicine, Danzhi decoction, on the expression angiogenesis factors in human endometrial cells during the sequelae of pelvic inflammatory disease (SPID) and explore the role of Danzhi decction in improving the blood stasis microenvironment of SPID. Methods A three-dimensional (3D) co-culture system including human vascular endothelial cells (VECs), endometrial stromal cells and glandular epithelial cells was established in vitro and treated with Danzhi decoction, sterilized water and aspirin respectively. A Milliplex multifunctional liquid chip technique was used to measure the expression levels of vascular endothelial growth factor (VEGF)-A/C/D, fibroblast growth factor −1/2, angiopoietin-2, epidermal growth factor (EGF), HB-EGF, bone morphogenetic protein-9, endoglin, endothelin-1, granulocyte colony stimulating factor, hepatocyte growth factor, interleukin-8, follistatin, placenta growth factor and leptin. The location of angiogenesis factors was monitored by immunofluorescence labeling and confocal laser scanning microscope 3D reconstruction. Results Endometrial stromal cells and glandular epithelial cells were isolated and primary cultured for establishing a 3D co-culture system. The levels of VEGF-A/C/D in Danzhi decoction group and aspirin group were significantly lower than those in mock group ( P <0.05), while there was no significant difference between Danzhi decoction group and aspirin group ( P >0.05). Furthermore, the alterative location of VEGF-A/C/D was observed in the cytoplasm of endometrial glandular epithelial cells. Conclusions Danzhi decoction may inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell. [ABSTRACT FROM AUTHOR]

Background: Recombinant human erythropoietin (rh-EPO) has been used as a drug to treat premature infant anemia for over a decade. In addition to its erythropoietic effect, rh-EPO has also been reported to have protective effects against brain injury. Objectives: Our aim was to evaluate the levels of angiogenesis-related cells (CD34+ cells) and angiogenic factors (vascular endothelial growth factor, VEGF, and angiopoietin-1, Ang-1) in a neonatal rat model of cerebral unilateral hypoxia-ischemia (HI) and to identify the effects of rh-EPO on angiogenic responses. Methods: Postnatal day 3 (PD3) rats underwent permanent ligation of the right common carotid artery followed by 6% O2 for 4 h (HI) or sham operation and normoxic exposure (sham). Immediately after HI, the rats received a single intraperitoneal injection of rh-EPO (5 U/g) or saline. Angiogenesis-related cells (CD34+ cells) and angiogenic factors (VEGF and Ang-1) were examined on PD5, 7, 10 and 14. Results: Compared with the sham rats, the number of CD34+ cells in HI rats increased from PD5 to 7 but decreased from PD10 to 14. VEGF and Ang-1 mRNA levels both increased from PD5 to 14. CD34+ cells, VEGF and Ang-1 were all upregulated in rh-EPO-treated rats compared with HI rats. Conclusions: In the present study, we show the angiogenic effects of rh-EPO in a rat model of neonatal cerebral unilateral HI. Our results highlight the powerful therapeutic potential of rh-EPO treatment of HI premature brain for the enhancement of angiogenic responses. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The Wnt/β-catenin signaling pathway plays a key role during hepatocellular carcinoma (HCC) genesis and development. The present study aimed to investigate the effects of the Wnt/β-catenin signaling pathway on the expression of angiogenic growth factors involved in HCC. The HCC HepG2 cell line was transfected with small interfering RNA (siRNA) against β-catenin. After 72 and 96h, protein was extracted and the expression levels of β-catenin, matrix metalloproteinase(MMP)-2, MMP-9, vascular endothelial growth factor(VEGF)A, VEGF-C and basic fibroblast growth factor(bFGF) were detected by western blot analysis. β-catenin protein expression was inhibited at both time points. Notably, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF protein expression levels decreased at 72h and then increased at 96 h after transfection. Our results demonstrated that in HCC cells, the Wnt/β-catenin signaling pathway may regulate the protein expression of the angiogenic factors, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF. These proteins were downstream of β-catenin signaling and were also regulated by other factors. In conclusion, the Wnt/β-catenin signaling pathway may contribute to the regulation of HCC angiogenesis, infiltration and metastasis through regulating the expression of these angiogenic factors. [ABSTRACT FROM AUTHOR]

Increasing importance is given to the clinical significance of the new formation of vessels (angiogenesis) in the course of physiological inflammatory and neoplastic processes. Angiogenesis is best studied in the growth of malignant tumors, since cancer may be regarded as the most important angiogenesis-dependent disease. Vascular endothelial cell proliferation, migration, and capillary formation are stimulated by angiogenic growth factors, which include the proteins vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor, and eicosanoids synthesized from n-6 fatty acids. Angiogenesis plays an important role in physiological proliferation of the endometrium and formation of corpus luteum in the second half of menstrual cycle. The present study showed that microvessel counts affect prognosis of patients with endometrial cancer. Analysis of angiogenesis in endometrial cancer may be a useful biologic parameter and additional study of neovascularization is required. Tumor angiogenesis is regulated by the balance of stimulators (e.g., VEGF, bFGF) and inhibitors of angiogenesis (e.g., angiostatin, endostatin, angiostatic steroids). Measuring angiogenesis (blood vessel density) and/or its main regulators such as VEGF and bFGF in solid tumors, or the levels of these growth factors in the serum or urine provides new and sensitive markers for tumor progression, metastasis and prognosis.

Age-related macular degeneration, pathologic myopia, ocular trauma, and other eye diseases can cause choroidal neovascularization (CNV). In recent years, photodynamic therapy (PDT), anti-vascular endothelial growth factor (anti-VEGF) medications, laser treatment, and other measures against CNV have been gradually applied in the clinical setting and in some cases have achieved good results. However, the pathogenesis of CNV has not been fully elucidated. The costimulatory system made up of cluster of differentiation 40 protein (CD40) and its ligand (CD40L) is an important signal transduction pathway among immune cells. The activation of CD40 can also stimulate the secretion of a variety of angiogenic growth factors (eg, VEGF) and basic fibroblast growth factors that might lead to CNV. The high level expression of CD40 and CD40L has been detected in CNV diseases. Interference with the CD40 signaling pathway may become a new target for CNV treatment. We review the relationship between CD40, CD40L, and CNV. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-α inhibitors. Methods: Inflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naïve patients or after the beginning of a therapy with a TNF-α inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2. Results: In the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (−44%; P =0.003) in comparison to a delayed decrease in the TNF-α inhibitor group after 6 weeks (−46%; P =0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P =0.7; r=−0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups. Conclusion: The decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF. [Copyright &y& Elsevier]

The article presents a study which demonstrated the possibility to transduce anti-angiogenic gene into aortic rings by adenovirus. An introduction to angiogenesis is offered. The role of two enzymatic families, namely the serine-proteases and matrix metalloproteases in angiogenesis is elucidated. The researchers concluded that the findings may be used for the treatment of angiogenesis-dependent diseases. Identified approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer.

Background: The expression of vascular endothelium growth factor (VEGF) has been correlated to the grading and stage of prostate cancers. However, data regarding Taiwanese prostate cancer patients are lacking. The aim of the present study was to examine VEGF expression in our radical prostatectomy specimens. Methods: Fifty-one radical prostatectomy specimens with prostate cancer (15 stage pT2N0, 25 pT3N0, 11 pT2-4 N1) were stained using goat anti-human VEGF polyclonal antibody (AB-293NA; R&D Systems Inc., Minneapolis, MN, USA). The VEGF expression in malignant and nonmalignant prostate tissues was compared. The correlations of VEGF immunoreactivity with Gleason scores and pathologic stages were examined. Mann–Whitney U test was used for comparison of preoperative prostate-specific antigen levels between patients with and without VEGF expression. Results: Positive VEGF staining was observed in 80.4% of malignant epithelia, 39.2% of peritumoral stroma, 68.6% of benign hyperplastic glands, and 25.5% of adjacent stroma. There was no difference in VEGF expression between malignant and nonmalignant areas. Advanced disease had significantly higher frequency of stroma but not epithelium VEGF staining as compared to organ-confined disease (p = 0.002 and p = 0.412, respectively). The Gleason 7 and higher tumors had significantly higher frequency of VEGF staining in stroma but not glandular epithelium (p = 0.041 and p = 0.353, respectively). Tumors with positive epithelium VEGF staining had significantly higher PSA levels (21.3 ± 18.1 vs. 10.8 ± 6.8 ng/mL; p = 0.013). Conclusion: There was no difference in VEGF immunoreactivity between malignant and benign prostatic epithelium in Taiwanese. High Gleason grade tumors and advanced disease had significantly higher frequency of VEGF expression in stroma but not glandular epithelium. Tumors with positive epithelium VEGF staining had significantly higher PSA levels. [Copyright &y& Elsevier]

The major vascular endothelial growth factor (VEGF) isoforms are splice variants from a single gene that differ in their extent of heparin affinity due to the absence of the heparin binding domain in the smallest isoform (mouse VEGF120, human VEGF121). A long-held assumption that has guided the use of VEGF isoforms clinically has been that their differences in heparin binding dictate their ability to diffuse through tissue, with VEGF121 moving most freely and that the distribution of recombinant VEGF would have therapeutically relevant consequences. To test this assumption, we delivered the genes encoding these isoforms by myoblast-mediated gene transfer, a means of delivering genes to highly localized sites within muscle. Surprisingly, all isoforms induced comparable extremely localized physiological effects. Significantly, irrespective of the isoform delivered, the vessels passing within several micrometers of muscle fibers expressing VEGF displayed sharply delineated changes in morphology. The induction of capillary wrapping around VEGF-producing fibers, and of vascular malformations in the muscle at high levels, did not differ among isoforms. These results indicate that heparin binding is not essential for the localization of VEGF in adult tissue and suggest that the preferential delivery of VEGF121 cDNA for clinical applications may not have a physiological basis. [ABSTRACT FROM AUTHOR]

To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells (107/mL) through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue (2 mL/kg) was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Tumor had significantly higher BV, BF and PS ( P=0.000) than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 ( P<0.01). Significant linear correlation was found between MVD and BV ( r=0.915, P=0.000), MVD and BF ( r=0.901, P=0.000), and MVD and PS ( r=0.459, P=0.042). We also found a rank correlation between PS and blue stain of tumor ( r s =0.861, P=0.000). Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor. [ABSTRACT FROM AUTHOR]

Objective: Women who are carrying a trisomy 13 fetus are more prone to develop preeclampsia. Excess circulating soluble fms-like tyrosine kinase-1 has been implicated recently in the pathogenesis of preeclampsia. Since the fms-like tyrosine kinase-1/soluble fms-like tyrosine kinase-1 gene is located on chromosome 13q12, we hypothesized that the extra copy of this gene in trisomy 13 may lead to excess circulating soluble fms-like tyrosine kinase-1, reduced free placental growth factor level, and increased soluble fms-like tyrosine kinase-1/placental growth factor ratio. This may then contribute to the increased risk of preeclampsia that has been observed in these patients. Our objective was to characterize the maternal circulating angiogenic proteins in trisomy 13 pregnancies. Study design: Maternal serum samples of trisomy 13, 18, 21 and normal karyotype pregnancies were obtained from first and second trimester screening programs. We chose 17 cases of trisomy 13 that were matched for maternal age, freezer storage time, and parity with 85 normal karyotype control samples. Additionally, 20 cases of trisomy 18 and 17 cases of trisomy 21 were included. Cases and control samples were assayed for levels of soluble fms-like tyrosine kinase-I and placental growth factor by enzyme-linked immunosorbent assay in a blinded fashion. Because of the skewed distributions of soluble fms-like tyrosine kinase-1 and placental growth factor, nonparametric analytic techniques were used, and the results are reported as median and ranges. Results: In early pregnancy trisomy 13 cases and control samples, the median circulating soluble fms-like tyrosine kinase-1/placental growth factor ratios were 17.0 (range, 1.2–61.3) and 6.7 (range, 0.8–62.9), respectively (P = .003). The median soluble fms-like tyrosine kinase-1/placental growth factor ratios in trisomy 18 and 21 were 4.8 (range, 0.9–53.9) and 5.1 (range, 1.0–18.1), which were not significantly different than the control samples. Furthermore, the differences between trisomy 13 and control samples were more pronounced in the second trimester specimens than in the specimens from the first trimester. Conclusion: These data suggest that alterations in circulating angiogenic factors may be involved intimately in the pathogenesis of preeclampsia in trisomy 13. A larger clinical study that measures these factors longitudinally and correlates them with pregnancy outcomes is needed to further establish the link between trisomy 13, altered angiogenic factors, and preeclampsia. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine the effects of outer membrane vesicles (OMV) obtained from Porphyromonas gingivalis (Pg) on the growth and function of human gingival fibroblasts (HGF) and human umbilical vein endothelial cells (HUVEC). Methods: OMV were obtained from a cell-free growth medium of Pg ATCC 33277 by 40% NH2SO4 precipitation and ultracentrifugation. Cell proliferation was measured by ³H-thymidine incorporation into growing HGF and HUVEC. Endothelial cell function was determined by their capacity to form a network of capillary tubes on an extracellular matrix (ECM). Results; Proliferating HGF and HUVEC demonstrated a significant dose-dependent inhibition of ³H-thymidine uptake when cultured with 0 to 40 µg/ml of OMV protein. HGF and HUVEC showed an IC50 of growth of about 9.0 µg/ml and 4.5 µg/ml of OMV protein, respectively. Capillary tube formation by HUVEC cultured on an ECM was suppressed by 70% to 80% with 5 µg/ml OMV protein after 18 hours of incubation. The presence of proteolytic enzymes in the OMV did not contribute to capillary tube disruption, since blocking enzyme activity with specific inhibitors did not reduce the suppression of capillary tube formation. After heating at 90°C for 5 minutes, OMV significantly lost their capacity to suppress capillary tube formation. Conclusions: OMV significantly inhibit the proliferation of cultured HGF and HUVEC in a dose-dependent manner. OMV suppressed the capillary tube formation by cultured HUVEC. The factor(s) appeared to be a protein and not endotoxin because its inhibitory activity was markedly reduced by heat inactivation. These studies suggest that OMV contribute to chronic periodontitis by suppressing cell proliferation and revascularization in periodontal tissues. [ABSTRACT FROM AUTHOR]

: Rationale and objectivesThe aim was to evaluate functional computed tomography (fCT) in the quantification of angiogenesis by comparing the tissue perfusion parameters measured by CT perfusion (CTP) software with histologic vascular parameters in a Matrigel model in rats. It was hypothesized that tissue perfusion parameters and histologic vascular parameters are related.: Materials and methodsIn vivo angiogenesis assays were performed using Matrigel supplemented with escalating doses (0 ng [control group], 250 ng, and 1,000 ng) of recombinant rat vascular endothelial growth factor (VEGF164) subcutaneously injected into the backs of Sprague Dawley rats. On day 7, rats with Matrigel plug underwent fCT following a bolus injection of iodinated contrast medium. Using CTP software, fCT parameters were generated (blood flow [BF], blood volume [BV], mean transit time, and permeability-surface area product) and functional maps on the basis of a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The animals were then sacrificed. Matrigel plug was sectioned into slices corresponding to the CT scan plane and stained with CD31 immunohistochemical stain. Histologic vascular parameters, including microvascular density (MVD), vessel number (VN), vascular area, and vascular perimeter, were measured. CTP and histologic parameters were correlated.: ResultsThe Matrigel plugs with the 1,000-ng VEGF group exhibited a higher MVD than the 250-ng VEGF and control groups (P <.05). VN differed significantly between the control versus the 250-ng VEGF groups and 250-ng versus 1,000-ng VEGF groups (P <.05), with the highest VN in the 250-ng VEGF group. BF, mean transit time, and permeability-surface area product each differed significantly to VEGF levels. Changes in BF and BV did not correspond with increases in MVD or VN; however, in the 250-ng VEGF group, there was a strong positive correlation (r = 0.9) between BV and VN, vascular area, and vascular perimeter, which was not seen in the control or 1,000-ng VEGF group. All fCT parameters significantly correlated with each other (P <.05), with strong correlations between BF and mean transit time (r = −0.7) and between BF and permeability-surface area product (r = 0.7) and a weak correlation between BF and BV (r = 0.3).: ConclusionThese results validate the VEGF-induced endothelial cell in a rat Matrigel model. In addition, histologic vascular parameter MVD does not correlate with fCT parameters measured by CTP software. [Copyright &y& Elsevier]

Objectives: To investigate whether concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in aspirated synovial fluid can be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis. Methods: bFGF and VEGF concentrations were measured in aspirated synovial fluid and serum samples from 66 patients with active arthritis (clinical diagnoses: rheumatoid arthritis (35 patients), psoriatic arthritis (9), reactive arthritis (11) and arthritis UNS (11)) utilizing commercial ELISA kits. Results: In comparison with controls, elevated concentrations of VEGF were found in synovial fluid compared with in serum in all forms of arthritis. There were no significant differences in synovial fluid bFGF or VEGF concentrations between rheumatoid arthritis and the other forms of inflammatory arthritis. Conclusion: Both serum bFGF and VEGF concentrations were increased in patients with rheumatoid arthritis. Patients treated with steroids had lower synovial fluid bFGF concentrations. Synovial fluid levels of bFGF and VEGF were elevated but could not be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis. [ABSTRACT FROM AUTHOR]