title: Regression of atherosclerosis is characterized by broad changes in the plaque macrophage transcriptome.
abstract: We have developed a mouse model of atherosclerotic plaque regression in which an atherosclerotic aortic arch from a hyperlipidemic donor is transplanted into a normolipidemic recipient, resulting in rapid elimination of cholesterol and monocyte-derived macrophage cells (CD68+) from transplanted vessel walls. To gain a comprehensive view of the differences in gene expression patterns in macrophages associated with regressing compared with progressing atherosclerotic plaque, we compared mRNA expression patterns in CD68+ macrophages extracted from plaque in aortic aches transplanted into normolipidemic or into hyperlipidemic recipients. In CD68+ cells from regressing plaque we observed that genes associated with the contractile apparatus responsible for cellular movement (e.g. actin and myosin) were up-regulated whereas genes related to cell adhesion (e.g. cadherins, vinculin) were down-regulated. In addition, CD68+ cells from regressing plaque were characterized by enhanced expression of genes associated with an anti-inflammatory M2 macrophage phenotype, including arginase I, CD163 and the C-lectin receptor. Our analysis suggests that in regressing plaque CD68+ cells preferentially express genes that reduce cellular adhesion, enhance cellular motility, and overall act to suppress inflammation.
authors: Division of Cardiology, and the 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.
authors: Jonathan E
authors: JE
authors: Feig
authors: Yuliya
authors: Y
authors: Vengrenyuk
authors: Vladimir
authors: V
authors: Reiser
authors: Chaowei
authors: C
authors: Wu
authors: Alexander
authors: A
authors: Statnikov
authors: Constantin F
authors: CF
authors: Aliferis
authors: Michael J
authors: MJ
authors: Garabedian
authors: Edward A
authors: EA
authors: Fisher
authors: Oscar
authors: O
authors: Puig
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; C081026:CD68 protein, mouse; D000097382:CD68 Molecule