文章基本信息

标题：Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload
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作者：Satoshi Okumura ; Gen Takagi ; Jun-ichi Kawabe 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：17
页码：9986-9990
DOI：10.1073/pnas.1733772100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The sympathetic nervous system is designed to respond to stress. Adenylyl cyclase (AC) is the keystone of sympathetic transmission, yet its role in response to acute overload in the heart or in the pathogenesis of heart failure is controversial. We examined the effects of pressure overload, induced by thoracic aortic banding, in mice in which type 5 AC, a major cardiac AC isoform, was disrupted (AC5-/-). Left ventricular weight/tibial length ratio (LVW/TL) was not different between the WT and AC5-/- at baseline and increased progressively and similarly in both groups at 1 and 3 wk after aortic banding. However, LV ejection fraction (LVEF) fell in WT at 3 wk after banding (from 70 {+/-} 2.8 to 57 {+/-} 3.9%, P < 0.05), and this decrease was associated with LV dilatation, indicating incipient cardiac failure. In contrast, AC5-/- mice did not exhibit a fall in LVEF from 74 {+/-} 2.2%. The number of apoptotic myocytes was similar at baseline, but it increased roughly 4-fold in WT at both 1 and 3 wk after banding, and significantly less, P < 0.05, in AC5-/-. Importantly, the increase in apoptosis occurred before the decline in LVEF in WT. The protective mechanism seems to involve Bcl-2, which was up-regulated significantly more in AC5-/- mice with pressure overload. Our findings suggest that limiting type 5 AC plays a protective role in response to pressure overload and the development of heart failure, potentially through limiting the incidence of myocardial apoptosis.