Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 17, Pages 9986-9990Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1733772100
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R37 HL033107, HL 67724, HL 65183, R01 HL033107, HL 61476, HL 33107, P01 HL069020, R01 HL067724, HL 59139, R01 HL065182, P01 HL059139, HL 59729, HL 69020, HL 65182] Funding Source: Medline
- NIA NIH HHS [R01 AG014121, AG 14121] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available