Human Arterial Smooth Muscle Cell Proliferation in Diabetes

Abstract

In the present study, we focus on the proliferation of human arterial smooth muscle cells (SMCs) from NIDDM patients (DM-SMCs) to clarify the reactivity to the growth factor(s) in fetal calf serum (FCS) and the factor(s) secreted by T-cells. The proliferation of DM-SMCs was significantly greater than SMCs from nondiabetic patients (nonDM-SMC). DM-SMC conditioned medium (DM-condMed) increased the growth of nonDM-SMCs. These results suggest that the growth factor is secreted from DM-SMCs as an autocrine system, which increases the proliferation of nonDM-SMCs. T-cells increased DNA synthesis of SMCs, and DM-SMCs strikingly reacted to T-cells. The present results support a function of T-cells in stimulating SMC growth. In conclusion, human arterial SMC proliferation is increased in diabetes in the same fashion as in experimentally induced diabetes in animals through responses to growth factors and an increased autocrine system. These results provide a mechanism for the increase in atherosclerotic disease in diabetes.

Hypoxia Stimulates Osteopontin Expression and Proliferation of Cultured Vascular Smooth Muscle Cells

“…Studies in experimental animal models of diabetes and in humans demonstrated enhanced proliferation of aortic VSM cells (19,20). Also, porcine aortic VSM cells in culture exhibit increased cell proliferation under hyperglycemic conditions (21).…”

“…Using this culture model, we reported that hypoxia induces proliferation, dedifferentiation, and/or extracellular matrix synthesis in cultured renal tubular epithelial and glomerular mesangial cells (16 -18). In the present study, we examined the effect of hypoxia on the proliferation of cultured rat aortic VSM cells to determine whether hypoxia directly alters their proliferative behavior.Enhanced proliferation of VSM cells has also been demonstrated in both human and experimental models of diabetes (19,20). In addition, cultured VSM cells grown in high media glucose concentration (to mimic hyperglycemia of diabetes) have exhibited increased cell proliferation (21).…”

“…Enhanced proliferation of VSM cells has also been demonstrated in both human and experimental models of diabetes (19,20). In addition, cultured VSM cells grown in high media glucose concentration (to mimic hyperglycemia of diabetes) have exhibited increased cell proliferation (21).…”

Hypoxia and high glucose upregulate AT1receptor expression and potentiate ANG II-induced proliferation in VSM cells

“…Others have shown that hypoxia is also mitogenic to cultured pulmonary artery smooth muscle and endothelial cells (12,13,25). Prevalence of tissue hypoxia and increased VSM cell proliferation is also reported in experimental models of diabetes and hypertension (1,10,28,35,40,45). Elevated glucose concentrations in medium have been shown to produce both hypertrophic and hyperplastic effects in cultured porcine aortic smooth muscle cells (32).…”

Effect of Glucose Concentration on Foam Cell Formation in THP-1 Cells

“…It has been reported that macrophages from diabetic patients showed accelerated cholesterol esterification when incubated in whole serum (8). We also have in vitro data that low density lipoprotein (LDL) obtained from diabetic patients strikingly simulated arterial smooth muscle cell-growth compared to LDL isolated from normal controls (9), and smooth muscle cells derived from diabetic patients proliferated more rapidly than those from normal subjects (10). In diabetes mellitus the function of arterial cells is altered by various factors.…”