|Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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.