Regulation of smooth muscle cell function by glycated polymerized type 1 collagen

患有糖尿病的患者和实验动物模型在动脉闭塞中发展侧支血管的能力较低。然而，糖尿病动脉生成受损的机制尚不清楚。在这项研究中，我们研究了糖化聚合1型胶原纤维（AGE-胶原）对血管平滑肌细胞（SMC）功能的影响。与天然胶原相比，AGE-胶原显著抑制了随机或PDGF引导的SMC迁移。通过对AGE-胶原的北方或西方印迹分析的整合素表达分析显示，与天然胶原相比，α2整合素的水平被显著抑制。相反，αv整合素在AGE-胶原上显著上调。AGE-胶原候选受体阻断抗体对SMC在AGE-胶原上迁移的影响表明，αv整合素阻断剂不能恢复SMC在AGE-胶原上的迁移，而CD 36抑制剂则能恢复SMC在AGE-胶原上的迁移。此外，血管内皮生长因子和基质金属蛋白酶-2，促血管生成因子的表达，抑制AGE-胶原蛋白，而血小板反应蛋白-1，抗血管生成因子，上调。因此，受损的SMC迁移和动态改变的表达血管生成调节剂的AGE-胶原可能有助于减少侧支血管的形成在糖尿病。

Patients and experimental animal models with diabetes have a lesser ability to develop collateral blood vessels in arterial occlusion. However, the mechanism underlying impaired arteriogenesis in diabetes is unclear. In this study, we examined the effects of glycated polymerized type 1 collagen fibrils (AGE-collagen) on functions of vascular smooth muscle cells (SMC). Random or PDGF-directed SMC migration was markedly suppressed on AGE-collagen as compared with native collagen. Analyses of integrin expression by Northern or Western blot analysis on AGE-collagen revealed that the levels of α2 integrin was markedly suppressed as compared with native collagen. In contrast, αv integrin was significantly upregulated on AGE-collagen. The effects on SMC migration on AGE-collagen of blocking antibodies against candidate receptors for AGE-collagen revealed that not αv integrins blockade but CD36 inhibition restored SMC migration inhibited on AGE-collagen. Moreover, expression of vascular endothelial growth factor and matrix metalloproteinase-2, pro-angiogenic factors, was suppressed on AGE-collagen, while thrombospondin-1, an anti-angiogenic factor, was upregulated. Thus, impaired SMC migration and dynamic altered expression of angiogenesis regulators by AGE-collagen may contribute to decreased formation of collateral blood vessels in diabetes.