RNA Interference for Discoidin Domain Receptor 2 Attenuates Neointimal Formation

Objectives—Discoidin domain receptor 2 (DDR2) plays potential roles in the regulation of collagen turnover mediated by smooth muscle cells (SMCs) in atherosclerosis. Little is known about the function of DDR2 in vascular system. We investigated whether inhibition of DDR2 by small interfering RNA (siRNA) can reduce neointimal formation after arterial injury. Methods and Results—SMCs from thoracic aorta of adult Wistar rats were cultured. The carotid artery from adult Wistar rats was injured by balloon catheter. DDR2 significantly increased migration and proliferation of SMCs. DDR2 siRNA inhibited 86 % of DDR2 protein expression in cultured SMCs. DDR2 protein and mRNA expression significantly increased at 14 days after carotid injury. DDR2 siRNA significantly reduced DDR2 protein and mRNA expression induced by balloon injury. The immunohistochemical stain demonstrated that DDR2 siRNA decreased MMP2 protein labeling induced by balloon injury, a pattern similar to that of DDR2 protein labeling. Neointimal area was significantly increased after carotid injury and was significantly reduced by DDR2 siRNA. Conclusions—DDR2 increases migration and proliferation of SMCs, and expression of DDR2 in carotid artery significantly increases after injury. DDR2 siRNA attenuates neointimal formation after carotid injury. DDR2 may play a pivotal role in the pathogenesis of neointimal thickening after mechanical injury. (Arterioscler Thromb Vasc Biol. 2008;28:1447-1453