イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Adrenal cortex hypoxia modulates aldosterone production in heart failure.
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：10902104/0006291X
巻・号・頁	524(1),pp.184-189
著者・共著者	YAMASHITA Kaoru†, ITO Kentaro, ENDO Jin**, MATSUHASHI Tomohiro, KATSUMATA Yoshinori, YAMAMOTO Tsunehisa, SHIRAKAWA Kohsuke, ISOBE Sarasa, KATAOKA Masaharu, YOSHIDA Naohiro, GOTO Shinichi, MORIYAMA Hidenori, KITAKATA Hiroki, MITANI Fumiko, FUKUDA Keiichi, GODA Nobuhito, ICHIHARA Atsuhiro, SANO Motoaki*
発行年月	2020/03
概要	Plasma aldosterone concentration increases in proportion to the severity of heart failure, even during treatment with renin-angiotensin system inhibitors. This study investigated alternative regulatory mechanisms of aldosterone production that are significant in heart failure. Dahl salt-sensitive rats on a high-salt diet, a rat model of heart failure with cardio-renal syndrome, had high plasma aldosterone levels and elevated β3-adrenergic receptor expression in hypoxic zona glomerulosa cells. In H295R cells (a human adrenocortical cell line), hypoxia-induced β3-adrenergic receptor expression. Hypoxia-mediated β3-adrenergic receptor expression augmented aldosterone production by facilitating hydrolysis of lipid droplets though ERK-mediated phosphorylation of hormone-sensitive lipase, also known as cholesteryl ester hydrolase. Hypoxia also accelerated the synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase, thereby increasing the cholesterol ester content in lipid droplets. Thus, hypoxia enhanced aldosterone production by zona glomerulosa cells via promotion of the accumulation and hydrolysis of cholesterol ester in lipid droplets. In conclusion, hypoxic zona glomerulosa cells with heart failure show enhanced aldosterone production via increased catecholamine responsiveness and activation of cholesterol trafficking, irrespective of the renin-angiotensin system.
DOI	10.1016/j.bbrc.2020.01.088
PMID	31982132