The role of chemokines in hypertension and consequent target organ damage.
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Immune cells infiltrate the kidney, vasculature, and central nervous system during hypertension, consequently amplifying tissue damage and/or blood pressure elevation. Mononuclear cell motility depends partly on chemokines, which are small cytokines that guide cells through an increasing concentration gradient via ligation of their receptors. Tissue expression of several chemokines is elevated in clinical and experimental hypertension. Likewise, immune cells have enhanced chemokine receptor expression during hypertension, driving immune cell infiltration and inappropriate inflammation in cardiovascular control centers. T lymphocytes and monocytes/macrophages are pivotal mediators of hypertensive inflammation, and these cells migrate in response to several chemokines. As powerful drivers of diapedesis, the chemokines CCL2 and CCL5 have long been implicated in hypertension, but experimental data highlight divergent, context-specific effects of these chemokines on blood pressure and tissue injury. Several other chemokines, particularly those of the CXC family, contribute to blood pressure elevation and target organ damage. Given the significant interplay and chemotactic redundancy among chemokines during disease, future work must not only describe the actions of individual chemokines in hypertension, but also characterize how manipulating a single chemokine modulates the expression and/or function of other chemokines and their cognate receptors. This information will facilitate the design of precise chemotactic immunotherapies to limit cardiovascular and renal morbidity in hypertensive patients.
Published Version (Please cite this version)10.1016/j.phrs.2017.02.026
Publication InfoCrowley, Steven Daniel; & Rudemiller, Nathan P (2017). The role of chemokines in hypertension and consequent target organ damage. Pharmacol Res, 119. pp. 404-411. 10.1016/j.phrs.2017.02.026. Retrieved from https://hdl.handle.net/10161/13936.
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Associate 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