Short-term vascular smooth muscle cells with platelet-derived growth factor (PDGF)-BB and angiotensin II induces stimulation of [3H]thymidine incorporation without mitosis

Abstract

Growth factors such as the platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II) have been shown to induce vascular smooth muscle cell (VSMC) proliferation after long stimulation periods. Little is known though, about the effects of PDGF-BB and Ang II on VSMC proliferation after short stimulation periods. The purpose of our study was to examine whether a short term (3-60 min) stimulation of VSMC with PDGF-BB or Ang II is sufficient to induce cell proliferation. Incubation of VSMC with Ang II (100 nM) or PDGFBB (50 ng/ml) caused a significant increase in [3H]thymidine incorporation starting after a 3-min stimulation, while the cell counts required 32 and 8 h of stimulation, respectively. Mitogen-activated protein kinase activation reached a maximum at 5-10 min of PDGF-BB or Ang II stimulation. This study demonstrates that the growth-promoting effects of PDGF-BB and Ang II are strongly dependent on the length of the stimulation period and that while prolonged stimulation periods (>8-32 h) result in VSMC proliferation, short ones (3-60 min) result only in [3H]thymidine incorporation without an increase in cell count, a fact of considerable pathophysiological significance, considering that the time kinetics of growth factors in the VSMC microenvironment have not as yet been clarified.