Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 not only with decreased phospholamban protein expression but also with increased phospholamban phosphorylation by PKA activation. The ratio of phosphorylated ryanodine receptor 2 (RyR2) to RyR2 protein was increased, but the amount of phosphorylated RyR2 was unaffected. These data provide a possible mechanism by which adenylyl cyclase type VI (in contrast to other signaling elements associated with increased cAMP generation) has a salutary effect in the failing heart.
 ...
PMID:Adenylyl cyclase type VI corrects cardiac sarcoplasmic reticulum calcium uptake defects in cardiomyopathy. 1524 35

The rationale for gene transfer of adenylyl cyclase type VI (AC(VI)) for clinical congestive heart failure (CHF) is based on recent experimental studies that have extended from cultured cardiac myocytes to preclinical studies in animal models of CHF. Over the past several years substantial data have indicated an unexpected and pronounced favorable effect of AC(VI) expression in cardiovascular disease. Preclinical studies have shown that increased cardiac AC content improves left ventricular function and attenuates deleterious remodeling in the failing heart, and reduces mortality in heart failure and in acute myocardial infarction. A brief review of the preclinical studies that have examined changes associated with increased AC expression in the heart is presented here.
 ...
PMID:Adenylyl cyclase gene transfer in heart failure. 1713 99