Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic states - A possible explanation for impaired collateral formation in cardiac tissue
Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic states - A possible explanation for impaired collateral formation in cardiac tissue
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DOI：
10.1161/hc0302.102143
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发表时间：
2002-01-22
期刊：
影响因子：
37.8
通讯作者：
King, GL
中科院分区：
文献类型：
--
作者：
Chou, E;Suzuma, I;King, GL
背景-糖尿病患者心肌缺血时血管生成反应不足可导致侧支形成不良。然而，视网膜中过度的新生血管形成引起增殖性糖尿病视网膜病变。由于血管内皮生长因子（VEGF）是缺氧时表达的主要血管生成因子，因此我们对胰岛素抵抗和糖尿病状态下视网膜、肾小球、主动脉和心肌中VEGF及其受体的表达进行了表征。在糖尿病和胰岛素抵抗的非糖尿病大鼠中，心肌中的β-淀粉样蛋白显著降低40%至70%。与非糖尿病供体相比，在糖尿病患者的心室中观察到VEGF和VEGF-R2降低了两倍。与此相反，VEGF及其受体的表达增加2倍，在视网膜和肾小球糖尿病或胰岛素抵抗大鼠。糖尿病大鼠的胰岛素治疗使心脏和微血管组织的变化正常化。胰岛素增加VEGF mRNA的表达在培养的新生大鼠心肌cytos. Conclusions的结果首次证明，差异调节血管内皮生长因子及其受体之间存在微血管和心脏组织，这可以调节胰岛素。这些结果为胰岛素抵抗和糖尿病患者视网膜中伴随的毛细血管渗漏和新血管形成以及心肌侧支形成不足提供了潜在的解释。
Background-Inadequate angiogenic response to ischemia in the myocardium of diabetic patients could result in poor collateral formation. Yet, excessive neovascularization in the retina causes proliferative diabetic retinopathy. Since vascular endothelial growth factor (VEGF) is the major angiogenic factor expressed in response to hypoxia, we have characterized expression of VEGF and its receptors in retina, renal glomeruli, aorta, and myocardium in insulin-resistant and diabetic states.Methods and Results-The expression of mRNA and protein for VEGF and its receptors, VEGF-R1 and VEGF-R2, in the myocardium was decreased significantly by 40% to 70% in both diabetic and insulin-resistant nondiabetic rats. Twofold reductions in VEGF and VEGF-R2 were observed in ventricles from diabetic patients compared with nondiabetic donors. In contrast, expression of VEGF and its receptors were increased 2-fold in retina and glomeruli from diabetic or insulin-resistant rats. Insulin treatment of diabetic rats normalized changes in both cardiac and microvascular tissues. Insulin increased VEGF mRNA expression in cultured rat neonatal cardiac myocytes.Conclusions-The results documented for the first time that differential regulation of VEGF and its receptors exist between microvascular and cardiac tissues, which can be regulated by insulin. These results provide a potential explanation for concomitant capillary leakage and neovascularization in the retina and inadequate collateral formation in the myocardium of insulin-resistant and diabetic patients.