Catestatin (CST) is a key mediator of the immunoendocrine regulation of cardiovascular function

摘要: Objective: Hypertension (HTN) is a global pandemic, affecting more than one billion people. Although catestatin (CST), chromogranin A (CgA)-derived peptide, decreases blood pressure (BP) in rodent models of HTN, the mechanisms underlying its hypotensive action yet to be established. Here we generated CST knockout (CST-KO) mice pinpoint mechanism CST. Methods and Results: CST-KO were hypertensive; their serum cytokines elevated, anti-inflammatory genes downregulated, hearts showed marked infiltration with macrophages. replenishment reversed all these phenotypes. It normalized BP, reduced cytokines, upregulated genes, cardiac infiltrates by approx 30%, as determined FACS. Pre-conditioning-induced cardioprotection was also abolished mice. We hypothesize that anti-hypertensive cardioprotective effects may caused suppressed trafficking macrophages heart inflammation. Such cause-and-effect relationship supported fact became normotensive when they depleted using chlodronate, or received bone marrow transplant from wild-type littermates. Mechanistically, tissue transcriptomes revealed multiple altered gene expression programs are commonly encountered human cardiomyopathies. Among others, prominent reduction Glo1 seen mice; supplementation increased it mora 7-fold. Because metabolizes methylglyoxal, an inflammatory agent whose accumulation promotes vascular damage HTN T2DM, this could means which attenuates inflammation improves cardiovascular health. Repletion improved glucose metabolism surface area mitochondrial cristae decreased secretion catecholamines; latter explains actions Conclusions: conclude mediated at least part via CST; absence CST, reactive, infiltrate alter ultrastructure, physiologic molecular makeup myocardium. These studies implicate key mediator observed crosstalk between systemic HTN.