INFLUENCE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN ON VASCULAR ANGIOTENSIN-II RECEPTOR EXPRESSION

Objectives To investigate the effect of oxidized low-density lipoprote in (LDL) on angiotensin type 1 (AT(1)) receptor expression and on angi otensin-induced mitogenesis in vascular smooth muscle cells. Design Si nce both LDL and the AT(1) receptor are thought to be involved in the pathogenesis of chronic vascular disease, we studied possible interact ions between these two biological systems in cultured rat vascular smo oth muscle cells. Recent studies have demonstrated that native LDL pro foundly increases the AT(1) receptor gene expression in vascular smoot h muscle cells. The present study was designed to show whether an oxid ative modification of LDL, which has been implicated as a major partic ipant in atherogenesis, has similar effects on vascular smooth muscle cells. Materials and methods Vascular smooth muscle cells isolated fro m rat thoracic aorta were cultured with oxidized LDL and assessed for their ability to synthesize DNA, and messenger (m)RNA expression, usin g Northern blot technology. Results Oxidized LDL had no significant ef fect on AT(1) receptor mRNA steady-state levels when incubated for 0-2 4 h. Moreover, oxidized LDL itself had no stimulatory effect on DNA sy nthesis in vascular smooth muscle cells, nor was the angiotensin II-in duced increase in DNA synthesis influenced by oxidized LDL. Conclusion s These data show that in contrast to native LDL, oxidized LDL has no effect on AT(1) receptor mRNA expression and no effect on angiotensin II-induced mitogenesis in vascular smooth muscle cells. (C) Rapid Scie nce Publishers.