Effects of growth factors on cytosolic free calcium concentration and DNA synthesis in cultured rat aortic smooth muscle cells

Proliferation of vascular smooth muscle cells (SMCs) has been considered to be an important process in the development of atherosclerosis. This study was conducted to investigate the role of cytosolic free calcium in DNA synthesis of SMCs stimulated by growth factors. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and somatomedin-C (Sm-C) increased [3H]thymidine incorporation, an index of DNA synthesis, and cell number of rat aortic SMCs after 36 hr of incubation. Cytosolic free calcium concentration [( Ca++]i) in quiescent SMCs, measured by using quin 2, was 178 +/- 18 nM (n = 15). Both PDGF and EGF provoked a rapid and transient rise in [Ca++]i, while Sm-C did not alter [Ca++]i. Nifedipine (3 X 10(-6) M) suppressed the rise in [Ca++]i provoked by PDGF and EGF. On the other hand, nifedipine suppressed the enhancement of DNA synthesis provoked by EGF, but did not suppress those by PDGF and Sm-C. These results suggest that the transient rise in [Ca++]i plays an important role in the proliferation of SMCs stimulated by EGF, while the rise in [Ca++]i is not involved in the mechanism of proliferation of SMCs provoked by Sm-C. The role of cytosolic free calcium in the proliferation of SMCs provoked by Sm-C. The role of cytosolic free calcium in the proliferation of SMCs provoked by PDGF was not definitive.