Influence of oxidized low-density lipoprotein on vascular angiotensin II receptor expression.

Abstract

To investigate the effect of oxidized low-density lipoprotein (LDL) on angiotensin type 1 (AT1) receptor expression and on angiotensin-induced mitogenesis in vascular smooth muscle cells. Since both LDL and the AT1 receptor are thought to be involved in the pathogenesis of chronic vascular disease, we studied possible interactions between these two biological systems in cultured rat vascular smooth muscle cells. Recent studies have demonstrated that native LDL profoundly increases the AT1 receptor gene expression in vascular smooth muscle cells. The present study was designed to show whether an oxidative modification of LDL, which has been implicated as a major participant in atherogenesis, has similar effects on vascular smooth muscle cells. Vascular smooth muscle cells isolated from rat thoracic aorta were cultured with oxidized LDL and assessed for their ability to synthesize DNA, and messenger (m)RNA expression, using Northern blot technology. Oxidized LDL had no significant effect on AT1 receptor mRNA steady-state levels when incubated for 0-24 h. Moreover, oxidized LDL itself had no stimulatory effect on DNA synthesis in vascular smooth muscle cells, nor was the angiotensin II-induced increase in DNA synthesis influenced by oxidized LDL. These data show that in contrast to native LDL, oxidized LDL has no effect on AT1 receptor mRNA expression and no effect on angiotensin II-induced mitogenesis in vascular smooth muscle cells.