Growth factors and their interaction in the regulation of vascular cells : with special reference to diabetes

Sammanfattning: Proliferation of vascular smooth muscle cells plays an important role in the development of atherosclerosis and in restenosis following balloon angioplasty. This study focuses on growth factors associated with diabetic vascular disease and their interaction in the regulation of vascular smooth muscle cell growth.The effect of streptozotocin-induced diabetes on proliferation of cells in aortic media two days after balloon angioplasty was studied. All proliferating cells in the aortic media were smooth muscle cells. In diabetic rats, the amount of proliferating cells was lower than in control rats. This was not accompanied by a change of transforming growth factor-ß1 (TGF-ß1) gene expression. Total TGF-ß1 levels in serum of diabetic rats was slightly lower and might possibly contribute to the inhibited proliferation of smooth muscle cells.The effect of angiotensin II on platelet-derived growth factor-BB(PDGF-BB)-induced growth was studied in cultured rat vascular smoothmuscle cells. Angiotensin II, acting through the AT1 receptor, transientlyinhibited the growth effect of PDGF-BB for approximately 6 hours. Thiswas not due to an autocrine effect of TGF-ß1, a growth factor consideredto mediate growth inhibitory actions of angiotensin II. Inhibition wasneither due to inhibition of PDGF-ß receptor phosphorylation.Large vessel endothelial cells from bovine aorta were shown to express and secrete insulin-like growth factor binding proteins (IGFBPs). Vascular endothelial growth factor (VEGF) and TGF-ß1, both associated with diabetic vascular complications, modulated the expression of IGFBPs in a way that might suggest increased bioavailability of insulin-like growth factor-I (IGF-I) locally in the vessel wall. VEGF, which is highly specific for endothelial cells, and TGF-ß1, might in this way indirectly regulate smooth muscle cell growth.In conclusion, we have shown that experimental diabetes has an inhibitory effect on smooth muscle cell proliferation in vivo, that interaction of growth factors, as shown for angiotensin II and PDGF-BB, might be of great importance for regulation of smooth muscle cell growth and that VEGF and TGF-ß1 regulate the IGF-system in large vessel endothelial cells with possible implications for regulation of smooth muscle cell function.