Author + information
- Received September 4, 2007
- Revision received January 7, 2008
- Accepted January 10, 2008
- Published online April 15, 2008.
- N. Chin Lai, PhD⁎,†,
- Tong Tang, PhD⁎,†,
- Mei Hua Gao, PhD⁎,†,
- Miho Saito, MD⁎,
- Toshiyuki Takahashi, MD, PhD⁎,
- David M. Roth, MD, PhD†,‡ and
- H. Kirk Hammond, MD⁎,†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. H. Kirk Hammond, VA San Diego Healthcare System (111A), 3350 La Jolla Village Drive, San Diego, California 92161.
Objectives This study sought to evaluate whether increased left ventricular (LV) adenylyl cyclase VI (ACVI) expression, at a time when severe congestive heart failure (CHF) was present, would increase function of the actively failing heart.
Background Increased LV ACVI content markedly reduces mortality and increases LV function after acute myocardial infarction (MI) in mice. However, the effects of increased cardiac ACVI content in the setting of severe heart failure caused by ischemic cardiomyopathy are unknown.
Methods Mice with cardiac-directed and regulated expression of ACVI underwent coronary artery ligation to induce severe CHF 5 weeks later. ACVI expression was then activated in 1 group (AC-On) but not the other (AC-Off). Multiple measures of LV systolic and diastolic function were obtained 5 weeks later, and LV samples were assessed for alterations in calcium and beta-adrenergic receptor signaling, apoptosis, and cardiac troponin I phosphorylation.
Results The LV systolic and diastolic function was increased 5 weeks after activation of ACVI expression. Improved LV function was associated with normalization of cardiac troponin I phosphorylation and reduced apoptosis.
Conclusions Activation of cardiac ACVI expression in mice with ischemic cardiomyopathy and severe CHF improves function of the failing heart.
This work was supported by National Institutes of Health grants 5P01HL066941, HL088426, and HL081741 (Dr. Hammond), Merit Review Awards from the Department of Veteran’s Affairs (Drs. Roth and Hammond), a Grant-in-Aid from the American Heart Association Western States Affiliate (Dr. Gao), and a fellowship from the Banyu Life Science Foundation International (Dr. Takahashi). Drs. Lai and Tang contributed equally to this work. Lynne Warner Stevenson, MD, served as Guest Editor for this article.
- Received September 4, 2007.
- Revision received January 7, 2008.
- Accepted January 10, 2008.
- American College of Cardiology Foundation