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Increased expression of adenylyl cyclase VI has beneficial effects on the heart, but strategies that increase cAMP production in cardiac myocytes usually are harmful. Might adenylyl cyclase VI have beneficial effects unrelated to increased beta-adrenergic receptor-mediated signaling? We previously reported that adenylyl cyclase VI reduces cardiac(More)
Sustained β-adrenergic receptor stimulation is associated with cardiomyopathy, an affect thought to result from cAMP-associated cardiac injury. Using a murine line with adenylyl cyclase 6 gene deletion (AC6KO), we tested the hypothesis that AC6 deletion, by limiting cAMP production, would attenuate cardiomyopathy in the setting of sustained β-adrenergic(More)
BACKGROUND Adenylyl cyclases (ACs) are a family of effector molecules for G-protein-coupled receptors. The 2 ACs most abundantly expressed in cardiac myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino acid homology. It has been speculated that coexpression of 2 AC types in cardiac myocytes represents redundancy, but the specific role of AC6 in(More)
OBJECTIVES This study sought to test the hypothesis that pressure stress of the adenylyl cyclase 6-deleted (AC6-KO) heart would result in excessive hypertrophy, early dilation and dysfunction, and increased fibrosis. BACKGROUND Cardiac-directed AC6 expression attenuates left ventricular (LV) hypertrophy and dysfunction in cardiomyopathy. METHODS AC6-KO(More)
Calcium malfunction plays a central role in heart failure. Here, we provide evidence that adenylyl cyclase type VI restores sarco(endo)plasmic reticulum 2a (SERCA2a) affinity for calcium and maximum velocity of cardiac calcium uptake by sarcoplasmic reticulum in murine dilated cardiomyopathy. Restoration of normal SERCA2a affinity for calcium is associated(More)
Cardiac-directed expression of adenylyl cyclase type VI (AC(VI)) increases stimulated cAMP production, improves heart function, and increases survival in cardiomyopathy. In contrast, pharmacological agents that increase intracellular levels of cAMP have detrimental effects on cardiac function and survival. We wondered whether effects that are independent of(More)
Cardiac-directed expression of AC6 has pronounced favorable effects on cardiac function possibly not linked with cAMP production. To determine rigorously whether cAMP generation is required for the beneficial effects of increased AC6 expression, we generated a catalytically inactive AC6 mutant (AC6mut) that has markedly diminished cAMP generating capacity(More)
Urocortin-2 (UCn2) peptide infusion increases cardiac function in patients with heart failure, but chronic peptide infusion is cumbersome, costly, and provides only short-term benefits. Gene transfer would circumvent these shortcomings. Here we ask whether a single intravenous injection of adeno-associated virus type 8 encoding murine urocortin-2(More)
We tested the hypothesis that deletion of adenylyl cyclase type V (AC(V)) would be associated with decreased left ventricular (LV) contractile function and responsiveness to beta-adrenergic receptor (betaAR) stimulation. Absence of cardiac AC(V) expression was confirmed by RT-PCR and immunoblotting in AC(V)-deleted mice (AC(V) (-/-)). Compared to sibling(More)
Congestive heart failure is associated with increased expression of pro-inflammatory cytokines, and the levels of these cytokines correlate with heart failure severity and prognosis. Chronic interleukin 6 (IL-6) stimulation leads to left ventricular (LV) hypertrophy and dysfunction, and deletion of IL-6 reduces LV hypertrophy after angiotensin II infusion.(More)