Phenotypic and Functional Heterogeneity of Macrophages and Dendritic Cell Subsets in the Healthy and Atherosclerosis-Prone Aorta

Abstract

Atherosclerosis continues to be the leading cause of cardiovascular disease. Development of atherosclerosis depends on chronic inflammation in the aorta and multiple immune cells are involved in this process. Importantly, resident macrophages and dendritic cells (DCs) are present within the healthy aorta, but the functions of these cells remain poorly characterized. Local inflammation within the aortic wall promotes the recruitment of monocytes and DC precursors to the aorta and micro-environmental factors direct the differentiation of these emigrated cells into multiple subsets of macrophages and DCs. Recent data suggest that several populations of macrophages and DCs can co-exist within the aorta. Although the functions of M1, M2, Mox, and M4 macrophages are well characterized in vitro, there is a limited set of data on the role of these populations in atherogenesis in vivo. Recent studies on the origin and the potential role of aortic DCs provide novel insights into the biology of aortic DC subsets and prospective mechanisms of the immune response in atherosclerosis. This review integrates the results of experiments analyzing heterogeneity of DCs and macrophage subsets in healthy and diseased vessels and briefly discusses the known and potential functions of these cells in atherogenesis.

Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

“…Depending on the stimulus, macrophages can differentiate into pro-inflammatory M1 macrophages, which are involved in cholesterol loading and produce factors that contribute to plaque rupture and thrombosis, or anti-inflammatory M2 macrophages, which synthesize matrix repair proteins that stabilize plaques [Shah et al 1995;De Paoli et al 2014]. The macrophage pool in atherosclerotic plaques is comprised of a complex mix of macrophage subsets and there is evidence, mainly from in vitro studies, to suggest that macrophage subsets exhibit phenotypic plasticity in response to various factors [Butcher and Galkina, 2012]. In mice, switching from the M2 (atheroprotective) to M1 (atherogenic) subtype within atherosclerotic lesions has been observed [Khallou-Laschet et al 2010].…”

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

“…In the heart, for example, resident macrophages express high levels of HO-1 and CD163 and directly interact with endothelial cells and cardiac myocytes (134). Tissue-resident MP may integrate signals from the surrounding tissue as part of a global network (37,98).…”

Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease

“…by guest www.bloodjournal.org From mainly induced by Th2 cytokines (IL-4, IL-10, IL-13). [41][42][43][44][45] These macrophage populations are functionally different: M1 cells have inflammatory functions and bactericidal activity and produce high levels of proinflammatory cytokines and reactive nitrogen and oxygen radicals; M2 cells have immunoregulatory functions, aid parasite clearance, show increased phagocytic activity, and are involved in cell growth control, matrix remodeling, angiogenesis, and tissue repair.…”