title: Activation of cardiac adenylyl cyclase expression increases function of the failing ischemic heart in mice.
abstract: OBJECTIVE
  This study sought to evaluate whether increased left ventricular (LV) adenylyl cyclase VI (AC(VI)) expression, at a time when severe congestive heart failure (CHF) was present, would increase function of the actively failing heart.
  
  
  BACKGROUND
  Increased LV AC(VI) content markedly reduces mortality and increases LV function after acute myocardial infarction (MI) in mice. However, the effects of increased cardiac AC(VI) content in the setting of severe heart failure caused by ischemic cardiomyopathy are unknown.
  
  
  METHODS
  Mice with cardiac-directed and regulated expression of AC(VI) underwent coronary artery ligation to induce severe CHF 5 weeks later. AC(VI) 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 AC(VI) expression. Improved LV function was associated with normalization of cardiac troponin I phosphorylation and reduced apoptosis.
  
  
  CONCLUSIONS
  Activation of cardiac AC(VI) expression in mice with ischemic cardiomyopathy and severe CHF improves function of the failing heart.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, USA.
authors.forename: N Chin
authors.initials: NC
authors.lastname: Lai
authors.forename: Tong
authors.initials: T
authors.lastname: Tang
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Gao
authors.forename: Miho
authors.initials: M
authors.lastname: Saito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: H Kirk
authors.initials: HK
authors.lastname: Hammond
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D003971:Diastole; D004789:Enzyme Activation; D006333:Heart Failure / Q000201:enzymology / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D051379:Mice; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta; D044169:Receptors, Calcium-Sensing; D012307:Risk Factors; D015398:Signal Transduction; D013599:Systole; D019210:Troponin I
chemical_list: D011943:Receptors, Adrenergic, beta; D044169:Receptors, Calcium-Sensing; D019210:Troponin I; D000262:Adenylyl Cyclases