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

Purpose: Patients with diabetes methods (DM) experience progressive macrova scular atherosclerosis and intimal hyper plastic restenosis with increased frequency as compared with nondiabetic patients. These observations suggest that vascular smooth muscle cells (VSMCs) behave in a phenotypically diffe rent and more aggressive manner in diabetic patients. In this study, we com pared 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 art ery, 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 dia betic patients had type 2 DM. Vascular specimens were obtained at the time of amputation from infragenicular arteries and during arterial revasculariz ation from saphenous veins. Cells from passages 2 and 3 were assayed for th eir proliferative capacity with total DNA fluorescence photometry and for a dhesion and migration with a modified Boyden chamber. Results: The average duration of diabetes was 11.6 +/- 4.1 years. The avera ge number of diabetic complications (retinopathy, neuropathy, nephropathy, coronary artery disease) was 2.8 +/- 0.7 per patient. Diabetic VSMCs exhibi ted abnormal morphology in cell culture with loss of the normal hill and va lley configuration. Proliferation was significantly increased in VSMCs of d iabetic origin (156 +/- 57 absorption units) as compared with those of nond iabetic origin (116 +/- 42 absorption units) (P < .001). Diabetic VSMCs dem onstrated significantly greater adhesion (63.6 +/- 24 per high-power field vs 37.9 +/- 13 per high-power field; P = .002) and migration (397 +/- 151 p er low-power field vs 121 +/- 99 per low-power field; P = .001) rates. Conclusions Diabetic VSMCs exhibit significantly increased rates of prolife ration, adhesion, and migration as well as abnormal cell culture morphology suggestive of abnormal contact inhibition. These observations of human VSM Cs in culture are consistent with ther increased rate of infragenicular ath erosclerosis and the increased rates of restenosis observed clinically in d iabetic patients. The atherosclerosis- and intimal hyperplasia-promoting be havior exhibited appears to be intrinsic to the DM-VSMC phenotype and must be considered when designing methods to limit atherosclerosis and intimal h yperplasia in diabetic patients.