Mitogenic Factors Released from Smooth Muscle Cells Are Responsible for Neointimal Cell Proliferation after Balloon Catheter Deendothelialization

Abstract

Smooth muscle cell (SMC) proliferation results in neointimal formation in response to selective deendothelialization. The neointimal SMC are characteristically different from normal, medial SMC. The major difference is that neointimal SMC have a higher proliferation rate. The high proliferation rate has been observed 15 weeks after endothelial injury. In this study, it is noted that neointimal SMC release some mitogenic factor(s) which is(are) responsible for inducing persistent SMC proliferation in an autocrine manner. The SMC were cultured from the media of normal rabbit aorta as well as the neointimal tissue formed 15 weeks after an endothelial injury. From the culture of the neointimal SMC, the conditioned medium was collected and growth factors, including PDGF-AB, TGF-β 1, TGF-β 2, and bFGF, were assayed. The conditioned medium was used to culture the medial SMC from normal rabbit aorta. The mitogenic effect of the conditioned medium was evaluated by the incorporation of [3H]thymidine into the SMC. Results demonstrated that PDGF-AB and TGF-β 1 were increased in neointimal SMC-conditioned medium. After incubation with the conditioned medium, medial SMC incorporated significantly higher [3H]thymidine, compared to incubation with control medium ( P ≤ 0.01). The data indicate that endothelial injury induces production of some growth factors, including PDGF and TGF-β, by the neointimal SMC. These growth factors may act in an autocrine manner to stimulate SMC proliferation for a long time following a single deendothelialization.