The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia

Objective—Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfamily C TRP (TRPC) channels requires the scaffolding protein Homer 1, which associates with the actin-binding protein Drebrin. We found that SMC Drebrin expression is upregulated in atherosclerosis and in response to injury and investigated whether Drebrin inhibits SMC activation, either through regulation of TRP channel function via Homer or through a direct effect on the actin cytoskeleton. Approach and Results—Wild-type (WT) and congenic Dbn−/+ mice were subjected to wire-mediated carotid endothelial denudation. Subsequent neointimal hyperplasia was 2.4±0.3-fold greater in Dbn−/+ than in WT mice. Levels of globular actin were equivalent in Dbn−/+ and WT SMCs, but there was a 2.4±0.5-fold decrease in filamentous actin in Dbn−/+ SMCs compared with WT. Filam...