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- W2101877864 abstract "Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt-induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathway, contributing to cardiac and renal damage. We studied the inflammatory response and tissue damage in rats treated with deoxycorticosterone acetate and high-salt diet (DOCA-salt), with or without mineralocorticoid receptor inhibition by spironolactone. To determine whether Th17 differentiation in DOCA-salt rats is caused by hypertension per se, DOCA-salt rats received antihypertensive therapy. In addition, to evaluate the pathogenic role of IL-17 in hypertension and tissue damage, we studied the effect of IL-17 blockade with a specific antibody (anti-IL-17). We found activation of Th17 cells and downregulation of forkhead box P3 mRNA in peripheral tissues, heart, and kidneys of DOCA-salt-treated rats. Spironolactone treatment prevented Th17 cell activation and increased numbers of forkhead box P3-positive cells relative to DOCA-salt rats. Antihypertensive therapy did not ameliorate Th17 activation in rats. Treatment of DOCA-salt rats with anti-IL-17 significantly reduced arterial hypertension as well as expression of profibrotic and proinflammatory mediators and collagen deposits in the heart and kidney. We conclude that mineralocorticoid receptor activation alters the Th17/regulatory T-lymphocyte/IL-17 pathway in mineralocorticoid-dependent hypertension as part of an inflammatory mechanism contributing to fibrosis." @default.
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- W2101877864 date "2014-04-01" @default.
- W2101877864 modified "2023-10-18" @default.
- W2101877864 title "Spironolactone Decreases DOCA–Salt–Induced Organ Damage by Blocking the Activation of T Helper 17 and the Downregulation of Regulatory T Lymphocytes" @default.
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- W2101877864 doi "https://doi.org/10.1161/hypertensionaha.113.02883" @default.
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