Mitogenic action of interleukin-1 alpha on vascular smooth muscle cells mediated by PDGF

We have investigated the effect of interleukin-1 (IL-1) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. Murine recombinant IL-1 alpha increased tritiated leucine incorporation into VSMC. IL-1 also stimulated tritiated thymidine uptake by VSMC in a dose-dependent manner. On the other hand, Ca2(+)-channel blocker, verapamil, inhibited the IL-1-induced thymidine uptake by VSMC with an IC50 of 10(-8) M. Antibody specific for platelet-derived growth factor (PDGF) also totally inhibited the IL-1-induced thymidine uptake. IL-1 showed no effects on the intracellular Ca2+ level in VSMC. Above results support the premise that IL-1 promotes the growth of VSMC via induction of endogenous PDGF production and might thus participate in the abnormal proliferation of VSMC that occurs early in atherogenesis.