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Objective: Coronary heart disease (CHD) is a disorder resulting from organic and functional coronary artery stenosis (CAS), thus causing reduced oxygenated blood in the heart. miRNAs are useful biomarkers in the diagnosis of atherosclerosis, CHD, and acute coronary syndrome. Vascular endothelial growth factor (VEGF) is closely related to CHD. This study explored the correlation of miR‐296 and VEGF‐B expression levels in peripheral blood with CAS degree in CHD patients. Methods: Totally 220 CHD patients were enrolled and classified into mild‐(71 cases)/moderate‐(81 cases)/severe‐CAS (68 cases) groups, with another 80 healthy cases as controls. The serum miR‐296 and VEGF‐B expression levels were detected using reverse transcription quantitative polymerase chain reaction. The correlation between miR‐296 and CAS‐related indexes was assessed via Pearson analysis. The binding relationship of miR‐296 and VEGF‐B was first predicted and their correlation was further analyzed via the Pearson method. The clinical diagnostic efficacy of miR‐296 or VEGF‐B on CAS degree was evaluated by the receiver operating characteristic curve. Results: Serum miR‐296 was downregulated in CHD patients and was the lowest in patients with severe‐CAS. miR‐296 was negatively‐correlated with high‐sensitivity C‐reactive protein, brain natriuretic peptide, and cardiac troponin I. miR‐296 targeted VEGF‐B. VEGF‐B was upregulated in CHD patients and inversely‐related to miR‐296. Low expression of miR‐296 and high expression of VEGF‐B both had high clinical diagnostic values on CAS degree in CHD patients. miR‐296 combined with VEGF‐B increased the diagnostic value on CAS. Conclusion: Low expression of miR‐296 combined with high expression of its target VEGF‐B predicts CAS degree in CHD patients. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) followed by refeeding, a phenomenon known as catch-up growth (CUG), results in excessive lipid deposition and insulin resistance in skeletal muscle, but the underlying mechanisms remain elusive. Recent reports have suggested that vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation by regulating endothelial fatty acid transport. Here, we found continuous activation of VEGF-B signaling and increased lipid uptake in skeletal muscle from CR to refeeding, as well as increased lipid deposition and impaired insulin sensitivity after refeeding in the skeletal muscle of CUG rodents. Inhibiting VEGF-B signaling reduced fatty acid uptake in and transport across endothelial cells. Knockdown of Vegfb in the tibialis anterior (TA) muscle of CUG mice significantly attenuated muscle lipid accumulation and ameliorated muscle insulin sensitivity by decreasing lipid uptake. Furthermore, we showed that aberrant histone methylation (H3K9me1) and acetylation (H3K14ac and H3K18ac) at the Vegfb promoter might be the main cause of persistent VEGF-B upregulation in skeletal muscle during CUG. Modifying these aberrant loci using their related enzymes [PHD finger protein 2 (PHF2) or E1A binding protein p300 (p300)] could regulate VEGF-B expression in vitro. Collectively, our findings indicate that VEGF-B can promote transendothelial lipid transport and lead to lipid overaccumulation and insulin resistance in skeletal muscle during CUG, which might be mediated by histone methylation and acetylation. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor B (VEGF-B) is a critical metabolic regulator in insulin resistance, and lipid distribution. We intended to ascertain the relationship between circulating VEGF-B and non-alcoholic fatty liver disease (NAFLD) in the general public. We recruited a total of 194 general participants for a routine physical health examination; of these, 84 participants were identified with NAFLD and 110 without NAFLD based on ultrasonographic findings. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), HbA1c, liver function, kidney function, plasma VEGF-B levels and indexes of metabolic syndrome (blood pressure, fasting plasma glucose, fasting lipids) were evaluated. Plasma VEGF-B values were significantly higher in individuals with NAFLD compared to those without NAFLD (P = 0.022), and analysis of covariance confirmed this result. VEGF-B showed a positive correlation with γ-glutamyl transpeptidase (γ-GT) and HOMA-IR in univariate analysis (q = 0.242; P = 0.001; q =0.174; P = 0.019, respectively). Multiple linear regression analysis showed that γ-GT and ALT were independently correlated with VEGF-B even after adjusted for gender and age (q = 0.286; P = 0.01; q =0.237; P = 0.033, respectively). Moreover, plasma VEGF-B showed a powerful correlation with blood pressure and renal dysfunction. Plasma VEGF-B might be a new clinical variable related to NAFLD and could be a proper biomarker for the early detection of hypertension and renal dysfunction. However, further studies with large cohorts’ size are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vascular endothelial growth factor B (VEGFB) is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the release of this surface-bound VEGFB, which triggers signaling pathways and gene expression to influence endothelial cell (autocrine action) and cardiomyocyte (paracrine effects) survival. Under conditions of hyperglycemia, when VEGFB production is impaired, a robust increase in vascular endothelial growth factor receptor (VEGFR)-1 expression ensues as a possible mechanism to enhance or maintain VEGFB signaling. However, even with an increase in VEGFR1 after diabetes, cardiomyocytes are unable to respond to VEGFB. In addition to the loss of VEGFB production and signaling, evaluation of latent heparanase, the protein responsible for VEGFB release, also showed a significant decline in expression in whole hearts from animals with chronic or acute diabetes. Defects in these numerous VEGFB pathways were associated with an increased cell death signature in our models of diabetes. Through this bidirectional interaction between endothelial cells (which secrete heparanase) and cardiomyocytes (which release VEGFB), this growth factor could provide the diabetic heart protection against cell death and may be a critical tool to delay or prevent cardiomyopathy. [ABSTRACT FROM AUTHOR]

Objectives: To prepare recombinant tPep-(vascular endothelial growth factor) VEGF-B and assess its biological activity. Results: This new VEGF fusion protein was constructed using a targeting peptide and prepared using E.coli. The tPep-VEGF-B was refolded from inclusion bodies and purified using affinity chromatography. Its bioactivity was determined in vitro using proliferation assay and wounding healing assay, and in vivo in zebrafish. By using the optimized downstream process, recombinant tPep-VEGF-B can be obtained with a purity of >90 % and a yield of 80 mg protein/l culture medium. The refolded protein is highly effective in promoting cell migration in vitro and in enhancing angiogenesis in vivo. Conclusion: We have constructed a new VEGF fusion protein with potential therapeutic application in treating metabolic diseases. [ABSTRACT FROM AUTHOR]

In recent years, studies have demonstrated that vascular endothelial growth factor B (VEGFB) can affect the metabolism of fatty acids and glucose, and it is expected to become a target for the diagnosis and treatment of metabolic diseases such as obesity and diabetes. At present, the specific mechanism that VEGFB regulates lipid and glucose metabolism balance is not completely understood. The present study used systemic VEGFB gene-knockout mice to investigate the effects of downregulation of the VEGFB gene on lipid metabolism and insulin secretion, and to explore the mechanism of the VEGFB pathway involved in the regulation of glucose and lipid metabolism. The morphological changes in the liver and pancreas of mice after VEGFB gene deletion were observed under a light microscope and a scanning electron microscope, and the effects of VEGFB gene deletion on lipid metabolism and blood glucose balance were detected by a serological technique. The detection indexes included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol. Simultaneously, fasting blood glucose, glycosylated hemoglobin A1c (HbA1c), fasting insulin and glucagon were measured. Insulin sensitivity was assessed by using the insulin tolerance tests and glucose tolerance tests, and function of β-cell islets was evaluated by using the insulin resistance index (HOMA-IR) and pancreatic β-cell secretion index (HOMA-β). Τhe protein expression changes of vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) in mouse islets were detected by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) after the VEGFB gene was knocked down to analyze the mechanism of VEGFB that may be involved in glucose and lipid metabolism. It was observed that after VEGFB was knocked down, mouse hepatocytes exhibited steatosis and increased secretory vesicles in islet cells. The lipid metabolism indexes such as TG, TC and LDL increased significantly; however, the levels of FBS, postprandial blood glucose and HbA1c decreased, whereas the glucose tolerance increased. Serum insulin secretion increased and HOMA-IR decreased since VEGFB was knocked down. Western blotting and RT-qPCR results revealed that the expression levels of VEGFR1 and neuropilin-1 decreased after the VEGFB gene was knocked down, while the expression levels of VEGFA and VEGFR2 increased. The absence of VEGFB may be involved in the regulation of glucose and lipid metabolism in mice by activating the VEGFA/VEGFR2 signaling pathway. VEGFB is expected to become a new target for the treatment of metabolic diseases such as obesity and diabetes. At present, the mechanism of VEGFB involved in regulating lipid metabolism and glucose metabolism is not completely clear. It was identified that downregulating VEGFB improved lipid metabolism and insulin resistance. The role of VEGFB/VEGFR1 pathway and other family members in regulating glucose and lipid metabolism was detected, which provided a theoretical and experimental basis for VEGFB to affect the regulation of glucose and lipid metabolism balance. [ABSTRACT FROM AUTHOR]

Aims Related transcription enhancer factor-1 (RTEF-1) has previously been demonstrated to play an important role in both endothelial cells and cardiomyocytes. However, the function of RTEF-1 in the communication between these two adjacent cell types has not been elucidated. Methods and results We have found that endothelium-specific RTEF-1 transgenic mice (VE-Cad/RTEF-1) developed significant cardiac hypertrophy after transverse aortic constriction surgery, as evidenced by an increased ratio of heart weight to tibia length, enlarged cardiomyocyte size, thickened left ventricular wall and elevated expression of hypertrophic gene markers, with up-regulation of vascular endothelial growth factor B (VEGF-B). Additionally, VEGF-B was increased in endothelial cells from VE-Cad/RTEF-1 mice, as well as in endothelial cells with forced RTEF-1 expression (HMEC-1/RTEF-1), and coincidentally decreased when RTEF-1 was deficient in HMEC-1. Using chromatin immunoprecipitation and luciferase assays, we found that RTEF-1 increased VEGF-B promoter activity through a direct interaction. Hypertrophy-associated genes and protein synthesis were up-regulated in cardiomyocytes that were incubated with conditioned medium from HMEC-1/RTEF-1 and the endothelial cells of VE-Cad/RTEF-1 mice. This effect could be abrogated by treating the myocytes with VEGF-B small interfering RNA and extracellular signal-regulated kinase 1/2 inhibitor. Conclusion Our data demonstrated that increased RTEF-1 in endothelial cells upregulates VEGF-B, which is able to stimulate hypertrophic genes in cardiomyocytes. These results suggest that the RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium. [ABSTRACT FROM PUBLISHER]