Platelet-Derived Growth Factor A-Chain Homodimer Stimulated Growth of Cultured Smooth Muscle Cells from Spontaneously Hypertensive Rats

Abstract

Vascular smooth muscle cells from spontaneously hypertensive rats (SHR) were growth stimulated when cocultured with bovine aortic endothelial cells whereas myoctyes from normotensive, Wistar Kyoto rats (WKY) were growth inhibited. The responsiveness of cells from the two rat sources to the two homodimeric forms of plateletderived growth factor (PDGF-AA or-BB) was different; SHR-derived cells responding equally well to both PDGF forms whereas cells from WKY responded to the B-chain homodimer only. The responses measured included S₆ kinase activation, phospholipase C mediated phosphoinositide catabolism and cell growth. Saturation binding experiments using [¹²⁵ I]-labelled PDGF homodimers (AA or BB) indicated that smooth muscle cells from hypertensive rats possess similar numbers of cell-surface A-chain receptors (α subunits) as Swiss 3T3 cells which have been used to characterize the mitogenic effects of the two PDGF homodimeric forms. The differences in responsiveness of SHR vs WKY cells to PDGF-AA and to the influence of endothelial cells may reside in their differential expression of PDGF receptors.

Key Words:

• Smooth muscle
• growth
• PDGF-AA
• PDGF receptor expression