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- W3126518562 abstract "ABSTRACT Hypertension (HTN) is associated with inflammation and excessive production of catecholamines. Hypertensive patients have reduced plasma levels of Catestatin (CST), a bioactive cleavage product of the prohormone Chromogranin A (CgA). In mouse models, HTN symptoms can be reduced by administration of CST, but the role of CST in the regulation of cardiovascular function is unknown. In this study, we generated mice with knockout (KO) of the region of the CgA gene coding for CST (CST-KO) and found that CST-KO mice are not only hypertensive as predicted, but also display left ventricular hypertrophy, have marked macrophage infiltration of the heart and adrenal gland, and have elevated levels of pro-inflammatory cytokines and catecholamines. Intraperitoneal injection with CST reversed these phenotypes, and ischemic pre-conditioning-induced cardioprotection was also abolished in CST-KO mice. Experiments with chlodronate depletion of macrophages and bone-marrow transfer showed that macrophages produce CST and that the anti-hypertensive effects of CST are mediated in part via CST’s immunosuppression of macrophages as a form of feedback inhibition. The data thus implicate CST as a key autocrine attenuator of the cardiac inflammation in HTN by reducing macrophage inflammation." @default.
- W3126518562 created "2021-02-15" @default.
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- W3126518562 date "2020-05-14" @default.
- W3126518562 modified "2023-09-26" @default.
- W3126518562 title "The immunosuppression of macrophages underlies the cardioprotective effects of catestatin (CST)" @default.
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- W3126518562 doi "https://doi.org/10.1101/2020.05.12.092254" @default.
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