Regulation of angiotensin AT(1) receptor gene expression during cell growth of vascular smooth muscle cells

Cell proliferation influences the expression of numerous tissue-specific genes. The angiotensin AT(1) receptor is highly expressed on vascular smooth muscle cells where it mediates cell contraction upon activation with angiotensin II. Since vascular smooth muscle cell de-differentiation leads to differential expression of several genes, we investigated the effects of cell growth on angiotensin AT(1) receptor gene expression in vascular smooth muscle cells in culture. Northern hybridization analysis revealed a decrease of angiotensin AT(1) receptor mRNA levels to approximately 20% in proliferating cells in comparison to growth-arrested cells. There is a correlative loss of membrane-associated angiotensin AT(1) receptor protein in growing cells versus non-growing cells, as assessed by saturation radioligand binding assays. In addition, the BB-isoform of platelet-derived growth factor (PDGF-BB), which induces proliferation of quiescent vascular smooth muscle cells, causes a marked down-regulation of angiotensin AT(1) receptor mRNA. These data suggest that proliferation of vascular smooth muscle cells leads to reduced angiotensin AT(1) receptor gene expression. The mechanisms underlying this process and its physiological implications remain to be defined.