Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration

Purpose: Patients with diabetes mellitus (DM) experience progressive macrovascular atherosclerosis and intimal hyperplastic restenosis with increased frequency as compared with nondiabetic patients. These observations suggest that vascular smooth muscle cells (VSMCs) behave in a phenotypically different and more aggressive manner in diabetic patients. In this study, we compared the in vitro rates of proliferation, adhesion, and migration of human VSMCs obtained from diabetic and nondiabetic patients. Methods: Human VSMC cultures were isolated from 23 diabetic patients (9 artery, 14 vein) and 15 nondiabetic patients (9 artery, 6 vein) with extensive lower extremity atherosclerosis. All patients were between 61 and 78 years of age (average: 68.4 years [diabetic]; 67.3 years [nondiabetic]). All diabetic patients had type 2 DM. Vascular specimens were obtained at the time of amputation from infragenicular arteries and during arterial revascularization from saphenous veins. Cells from passages 2 and 3 were assayed for their proliferative capacity with total DNA fluorescence photometry and for adhesion and migration with a modified Boyden chamber. Results: The average duration of diabetes was 11.6 ± 4.1 years. The average number of diabetic complications (retinopathy, neuropathy, nephropathy, coronary artery disease) was 2.8 ± 0.7 per patient. Diabetic VSMCs exhibited abnormal morphology in cell culture with loss of the normal hill and valley configuration. Proliferation was significantly increased in VSMCs of diabetic origin (156 ± 57 absorption units) as compared with those of nondiabetic origin (116 ± 42 absorption units) (P