The role of chemokines in hypertension and consequent target organ damage

Abstract

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.

Maternal undernutrition results in altered renal pro-inflammatory gene expression concomitant with hypertension in adult male offspring that is ameliorated following pre-weaning growth hormone treatment

“…33,34 Infiltrating leukocytes can also produce proinflammatory cytokines including TNF-α which further induce the expression of chemokines such as MCP-1 in resident tissue cells forming a positive feedback loop. 35 The current study provides some evidence of this with increased MCP-1 and adhesion molecule expression in the UN-S group which is associated with an increase in plasma TNF-α concentrations as well as renal mRNA expression. MCP-1 is associated with hypertensive conditions, and inhibiting its action reduces macrophage infiltration, normalizes blood pressure, prevented chronic renal damage and vascular inflammation in the hypertensive rat.…”

Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension

“…A number of previous studies have shown that the course of hypertension is accompanied by local and systemic inflammation [17][18][19] . The previous studies have found that H-type hypertension patients are more prone to have cerebral infarction, suggesting that Hcy has a high probability of causing ischemic strokes 20 .…”

Chemokine Receptor 5, a Double-Edged Sword in Metabolic Syndrome and Cardiovascular Disease

“…However, this finding is contrary to previous studies which have suggested that CCL5 plays an important protective role in hypertension-induced renal injury. In the angiotensin II-induced hypertension mice model, CCL5 gene deficiency exhibited markedly aggravation of kidney damage, macrophage infiltration, and proinflammatory cytokine expression, which led to the aggravation of urinary albumin excretion (Rudemiller and Crowley, 2017). This may be explained by the blockade of one chemokine leading to the upregulated expressions of other cytokines that exacerbate RASdependent hypertension, as CCL2 blockade abrogates the enhanced renal macrophage infiltration and interstitial fibrosis in CCL5deficient mice (Mikolajczyk et al, 2016;Rudemiller et al, 2016).…”