Regulation of smooth muscle cell accumulation in diabetes-accelerated atherosclerosis.
Diabetes leads to accelerated formation/progression of lesions of atherosclerosis. Cardiovascular disease thus develops earlier in people with type 1 or type 2 diabetes compared to people without diabetes, and cardiovascular (macrovascular) disease is the major cause of death in adults with diabetes. The molecular and cellular mechanisms leading to diabetes-accelerated atherosclerosis are not well understood. The arterial smooth muscle cell (SMC), one of the three or four principal cell types in atherosclerosis, has been extensively studied over the years. Proliferation and accumulation of SMCs are believed to play important roles in the progression of macrophage-rich lesions to fibroatheromas. Further progression of these atheromas into complicated vulnerable lesions that are likely to cause the acute clinical symptoms of atherosclerosis (myocardial infarction and stroke) may involve cell death and loss of SMCs from the fibrous cap of the lesion. Recent animal studies have shown that diabetes causes a marked increase in SMC accumulation and proliferation in atheromas. Hyperglycemia, advanced glycation end-products, insulin and lipid abnormalities associated with the diabetic environment have been suggested to increase SMC accumulation. Indeed, it is becoming increasingly clear that macrovascular disease associated with diabetes is a multifactorial disease. We review the factors and mechanisms that may regulate SMC proliferation and accumulation in different stages of lesion progression in diabetes. We propose that lipid abnormalities associated with diabetes can act in combination with growth factors present in the diabetic environment to increase SMC accumulation and accelerate lesion progression.
Askari
B
B
Department of Pathology, University of Washington, Box 35470, Seattle, WA 98195-7470, USA.
Renard
C B
CB
Bornfeldt
K E
KE
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D003920:Diabetes Mellitus / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D009130:Muscle, Smooth / Q000473:pathology*