The role of the adventitia in vascular inflammation.
Traditional concepts of vascular inflammation are considered "inside-out" responses centered on the monocyte adhesion and lipid oxidation hypotheses. These mechanisms likely operate in concert, holding the central tenet that the inflammatory response is initiated at the luminal surface. However, growing evidence supports a new paradigm of an "outside-in" hypothesis, in which vascular inflammation is initiated in the adventitia and progresses inward toward the intima. Hallmarks of the outside-in hypothesis include population of the adventitia with exogenous cell types, including monocytes, macrophages, and lymphocytes, the phenotypic switch of adventitial fibroblasts into migratory myofibroblasts, and increased vasa vasorum neovascularization. The resident and migrating cells deposit collagen and matrix components, respond to and upregulate inflammatory chemokines and/or antigens, and regulate the local redox state of the adventitia. B cells and T cells generate local humoral immune responses against local antigen presentation by foam cells and antigen presenting cells. These events result in increased local expression of cytokines and growth factors, evoking an inflammatory response that propagates inward toward the intima. Ultimately, it appears that the basic mechanisms of cellular activation and migration in vascular inflammation are highly conserved across a variety of cardiovascular disease states and that major inflammatory events begin in the adventitia.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, GA, USA. kathryn.maiellaro@bme.gatech.edu
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D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology; D003238:Connective Tissue / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D006973:Hypertension / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D017539:Tunica Intima / Q000276:immunology; D014657:Vasculitis / Q000276:immunology*