statins promote the regression of atherosclerosis via activation of the ccr7-dependent emigration pathway in macrophages他汀类药物促进动脉粥样硬化的回归通过激活巨噬细胞的ccr7-dependent移民途径.pdfVIP

Statins Promote the Regression of Atherosclerosis via Activation of the CCR7-Dependent Emigration Pathway in Macrophages 1 1 1 1 2 Jonathan E. Feig , Yueting Shang , Noemi Rotllan , Yuliya Vengrenyuk , Chaowei Wu , Raanan 1¤a 2¤b 1 1 Shamir , Ines Pineda Torra , Carlos Fernandez-Hernando , Edward A. Fisher *, Michael J. Garabedian2* 1 Division of Cardiology (Marc and Ruti Bell Program in Vascular Biology), Department of Medicine, New York University School of Medicine, New York, New York, United States of America, 2 Department of Microbiology, New York University School of Medicine, New York, New York, United States of America Abstract HMG-CoA reductase inhibitors (statins) decrease atherosclerosis by lowering low-density-lipoprotein cholesterol. Statins are also thought to have additional anti-atherogenic properties, yet defining these non-conventional modes of statin action remains incomplete. We have previously developed a novel mouse transplant model of atherosclerosis regression in which aortic segments from diseased donors are placed into normolipidemic recipients. With this model, we demonstrated the rapid loss of CD68+ cells (mainly macrophages) in plaques through the induction of a chemokine receptor CCR7-dependent emigration process. Because the human and mouse CCR7 promoter contain Sterol Response Elements (SREs), we hypothesized that Sterol Regulatory Element Binding Proteins (SREBPs) are involved in increasing CCR7 expression and through this mechanism, statins would promote CD68+ cell emigration from plaques. We examined whether statin