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.
Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis
Abbreviations used: Adv, adventitia; ANOVA, analysis of variance; DT, descending thoracic aorta; GC and LC, greater curvature and lesser curvature, respectively, of the ascending aortic arch; HRP, horseradish peroxidase; IAO, intercostal artery ostia; ICAM-2, intercellular adhesion molecule–2; LDL, low density lipoprotein; LOX-1, lectin-like oxidized LDL receptor–1; MCP-1, monocyte chemotactic protein–1; PI, propidium iodide; RAM, rabbit antimacrophage; VCAM-1, vascular cell adhesion molecule–1.
J. Jongstra-Bilen and M. Haidari contributed equally to this work.
M. Haidari's present address is Atherosclerosis Research Lab, Texas Heart Institute, Houston, TX 77030.
Jenny Jongstra-Bilen, Mehran Haidari, Su-Ning Zhu, Mian Chen, Daipayan Guha, Myron I. Cybulsky; Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis . J Exp Med 4 September 2006; 203 (9): 2073–2083. doi: https://doi.org/10.1084/jem.20060245
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionSee also
Email alerts
Advertisement