The role of macrophages in hypertension and its complications.
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Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent disease associated with catastrophic cardiovascular morbidity. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines induce endothelial and epithelial dysfunction, respectively, resulting in vascular oxidative stress and impairment of sodium excretion. By contrast, VEGF-C-expressing macrophages in the skin can facilitate the removal of excess interstitial stores of sodium by stimulating lymphangiogenesis. Inappropriate activation of the renin-angiotensin system (RAS) contributes to essential hypertension in a majority of patients, and macrophages express the type 1 (AT1) receptor for angiotensin II (Ang II). While proinflammatory macrophages clearly contribute to RAS-dependent hypertension, activation of the AT1 receptor directly on macrophages suppresses their M1 polarization and limits tubular and interstitial damage to the kidney during hypertension. Thus, stimulating the macrophage AT1 receptor ameliorates the target organ damage and immune stimulation provoked by AT1 receptor activation in intrinsic renal and vascular cells. The proinflammatory cytokines TNF-α and IL-1β produced by M1 macrophages drive blood pressure elevation and consequent target organ damage. However, additional studies are needed to identify the tissues in which these cytokines act and the signaling pathways they stimulate during hypertension. Moreover, identifying the precise myeloid cell subsets that contribute to hypertension should guide the development of more precise immunomodulatory therapies for patients with persistent blood pressure elevation and progressive end-organ injury.
Published Version (Please cite this version)10.1007/s00424-017-1950-x
Publication InfoJustin Rucker, A; & Crowley, Steven D (2017). The role of macrophages in hypertension and its complications. Pflugers Archiv : European journal of physiology, 469(3-4). pp. 419-430. 10.1007/s00424-017-1950-x. Retrieved from https://hdl.handle.net/10161/17181.
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Professor of Medicine
Our laboratory explores the contribution of the immune system and inflammatory mediators to the progression of target organ damage in the setting of cardiovascular disease. We are pursuing several related projects in this field:(1) The actions of type 1 angiotensin receptors on specific immune cell populations in hypertension, target organ damage, and tissue fibrosis.(2) Cell-specific actions of inflammatory cytokines in regulating blood pressure and end-organ injury.(3) Mechan