Targeting GGTase-I Activates RHOA, Increases Macrophage Reverse Cholesterol Transport, and Reduces Atherosclerosis in Mice

摘要: Background—Statins have antiinflammatory and antiatherogenic effects that been attributed to inhibition of RHO protein geranylgeranylation in inflammatory cells. The activity geranylgeranyltransferase type I (GGTase-I) is widely believed promote membrane association activation family proteins. However, we recently showed knockout GGTase-I macrophages activates proteins proinflammatory signaling pathways, leading increased cytokine production rheumatoid arthritis. In this study, asked whether the GGTase-I–deficient would influence development atherosclerosis low-density lipoprotein receptor–deficient mice. Methods Results—Aortic lesions mice lacking (Pggt1b▵/▵) contained significantly more T lymphocytes than controls. Surprisingly, however, mean atherosclerotic lesion area Pggt1b▵/▵ was reduced by ≈60%. deficiency acc...