Role of Monocytes in Atherogenesis

Abstract

This review focuses on the role of monocytes in the early phase of atherogenesis, before foam cell formation. An emerging consensus underscores the importance of the cellular inflammatory system in atherogenesis. Initiation of the process apparently hinges on accumulating low-density lipoproteins (LDL) undergoing oxidation and glycation, providing stimuli for the release of monocyte attracting chemokines and for the upregulation of endothelial adhesive molecules. These conditions favor monocyte transmigration to the intima, where chemically modified, aggregated, or proteoglycan- or antibody-complexed LDL may be endocytotically internalized via scavenger receptors present on the emergent macrophage surface. The differentiating monocytes in concert with T lymphocytes exert a modulating effect on lipoproteins. These events propagate a series of reactions entailing generation of lipid peroxides and expression of chemokines, adhesion molecules, cytokines, and growth factors, thereby sustaining an ongoing inflammatory process leading ultimately to lesion formation. New data emerging from studies using transgenic animals, notably mice, have provided novel insights into many of the cellular interactions and signaling mechanisms involving monocytes/macrophages in the atherogenic processes. A number of these studies, focusing on mechanisms for monocyte activation and the roles of adhesive molecules, chemokines, cytokines and growth factors, are addressed in this review.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

“…We also examined surface adhesion molecule expression on circulating monocytes by flow cytometry and on the aortic endothelium by immunohistochemistry, because several of these molecules have been shown to be critically important in monocyte recruitment into vessel walls (22,28,35,46). The selectin group of adhesion molecules are involved in monocyte rolling and tethering to activated endothelium, while the integrins (CD18/CD11, VLA-4) are required for firm adhesion to proteoglycans and immunoglobulin molecules (ICAM-1 and VCAM-1) on the vascular endothelium.…”

“…In the process of monocyte recruitment, changes in adhesion molecules on monocytes are involved in leukocyte tethering, rolling (E-and L-selectin), firm adhesion (CD11/CD18 integrins), and transmigration [very late antigen (VLA)-4, platelet endothelial cell adhesion molecule (PECAM)-1] by interacting with molecules on the endothelium [intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM) -1]. The expression of these various surface antigens is modulated by inflammatory cytokines (22,28,35,46).…”

LDL protein nitration: Implication for LDL protein unfolding

“…This notion is strengthened by the observation that posttranslational modifications of apoB100 are elevated in atherosclerotic lesions [5]. Oxidation of LDL can be carried out by transition metals, hemoglobin, myeloperoxidase, cerruloplasmin, and reactive oxygen species generated by vascular endothelium [6][7][8]. The oxidative modifications render the LDL particle electronegatively charged (LDL − ) as compared to native LDL (nLDL) [3,9,10].…”

Molecular Studies on Coronary Artery Disease—A Review

“…The increases in oxidation of LDL in persons who smoke promote monocyte adhesion and movement into the subintimal space. The continued stimulation of intimal cells by oxidized LDL leads to the advancement of atherosclerosis [39]. Tobacco smoke may cause insulin resistance, a risk factor for diabetes and CVD [40].…”