title: Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis.
abstract: Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule-1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow-derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1-deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Jongstra-Bilen
authors.forename: Mehran
authors.initials: M
authors.lastname: Haidari
authors.forename: Su-Ning
authors.initials: SN
authors.lastname: Zhu
authors.forename: Mian
authors.initials: M
authors.lastname: Chen
authors.forename: Daipayan
authors.initials: D
authors.lastname: Guha
authors.forename: Myron I
authors.initials: MI
authors.lastname: Cybulsky
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000033:anatomy & histology / Q000502:physiology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D022423:Myeloid Cells / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D017539:Tunica Intima / Q000166:cytology / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C480027:ICAM-2 protein, mouse