Platelet-Derived Growth Factor Mediates Angiotensin II-Induced DNA Synthesis in Vascular Smooth Muscle Cells

Abstract

In order to elucidate the mechanism of angiotensin II (ANG II)-induced proliferation in vascular smooth muscle cells in culture, growth rates and ³H-thymidine incorporation into DNA in response to ANG II treatment were examined in cultured rat aortic smooth muscle cells. ANG II-treated and control cells were exposed to the ANG II receptor antagonists [Sar¹, Val⁵, Ala⁸]-ANG II (Sar) and DUP753 and to antibody against platelet-derived growth factor (PDGF). In growing cells, ANG II acted as a moderate mitogen, inducing an increase in growth rate during the first two days of treatment. ANG II induced a marked increase in ³H-thymidine incorporation in cultured vascular smooth muscle cells. The effect was blocked by the ANG II inhibitors Sar and DUP753 and by the PDGF antibody. ANG II was able to stimulate vascular smooth muscle growth in cell culture. The effect seemed to be mediated, at least in part, by PDGF. These results are in agreement with a possible role of ANG II in promoting vascular growth in physiological and/or pathological situations.