Cardiac steroidogenesis and glucocorticoid in the development of cardiac hypertrophy during the progression to heart failure

• DOI: 10.1097/hjh.0b013e328326cb04
• Publication Date: 2009-05-21T13:01:49Z
• Authors: Tomohito Ohtani; Toshiaki Mano; Shungo Hikoso; Yasushi Sakata; Mayu Nishio; Yasuharu Takeda; Kinya Otsu; Takeshi Miwa; Tohru Masuyama; Masatsugu Hori; Kazuhiro Yamamoto
• Keywords: Corticosterone; Mineralocorticoid; Atrial natriuretic peptide

Background Elevated plasma glucocorticoid level is an independent predictor of increased mortality risk in chronic heart failure, but local biosynthesis and pathophysiological roles glucocorticoids the remain unclear. Methods Dahl salt-sensitive rats on high-salt diet mice with transthoracic aortic banding (TAC) operation (TAC mice), both which finally represent were assessed at compensatory hypertrophic stage. As a model cardiac-specific activation steroidogenesis, α-myosin heavy chain–steroidogenic acute regulatory protein transgenic used. Results In hypertrophied hearts TAC mice, gene expressions steroidogenic CYP11A, rate limiting factors steroid biosynthesis, significantly upregulated cardiac corticosterone was compared age-matched control. Although represented no morphological changes basal condition, induced greater increases ratio left ventricular weight to body (4.8 ± 0.2 vs.4.3 0.1 mg/g, P < 0.05) (104.5 13.3 vs. 69.8 3.8 pg/mg, than littermates. neonatal cardiomyocytes, atrial natriuretic peptide expression, synthesis cell surface area, provided additive effects phenylephrine-induced myocytes. These prevented by receptor blockade not mineralocorticoid blockade. Conclusion hearts, steroidogenesis activated increase level. Glucocorticoid had potential augmenting hypertrophy via even under α-adrenoceptor-mediated signaling. Cardiac system may play important development progression failure.