Rho-Associated Coiled-Coil-Containing Kinase 2 Deficiency in Bone Marrow–Derived Cells Leads to Increased Cholesterol Efflux and Decreased Atherosclerosis

Background—Macrophages play a central role in the development of atherosclerosis. However, the signaling pathways that regulate their function are not well understood. The Rho-associated coiled-coil-containing kinases (ROCK1 and ROCK2) are serine-threonine protein kinases that are involved in the regulation of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and bone marrow–derived cells mediates atherogenesis. However, a similar role for ROCK2 in the pathogenesis of atherosclerosis has not been determined. Methods and Results—The bone marrows from wild-type, ROCK2+/−, and ROCK2−/− mice were transplanted into irradiated recipient low-density lipoprotein receptor−/− mice, and atherosclerosis was induced with a 16-week high-cholesterol diet. Compared with wild-type bone marrow–transplanted mice, ROCK2+/− bone marrow–transplanted and ROCK2−/− bone marrow–transplanted mice showed substantially less lipid accumulation in the aorta (8.46±1.42% and 9.80±2.34% versus 15.64±1.89%; P<0.01 fo...