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 immunosuppression of macrophages by CST 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.

中文翻译：

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巨噬细胞的免疫抑制是catestatin（CST）的心脏保护作用的基础

高血压（HTN）与炎症和儿茶酚胺的过量产生有关。高血压患者血浆中Catestatin（CST）的水平降低，这是前激素Chromogranin A（CgA）的生物活性裂解产物。在小鼠模型中，可通过施用CST减轻HTN症状，但尚不清楚CST在调节心血管功能中的作用。在这项研究中，我们产生了具有编码CST（CST-KO）的CgA基因区域的敲除（KO）的小鼠，发现CST-KO小鼠不仅如预期的那样具有高血压，而且还表现出左心室肥大心脏和肾上腺的巨噬细胞浸润，并具有升高的促炎细胞因子和儿茶酚胺水平。CST腹腔注射逆转了这些表型，并且在CST-KO小鼠中也取消了缺血预处理引起的心脏保护作用。氯酸盐消耗巨噬细胞和骨髓转移的实验表明，巨噬细胞会产生CST，并且CST的抗高血压作用部分是通过CST对巨噬细胞的免疫抑制（作为一种反馈抑制形式）介导的。因此，数据表明CST通过减少巨噬细胞炎症而成为HTN中心脏炎症的关键自分泌减毒​​剂。