New signaling pathways associated with increased cardiac adenylyl cyclase 6 expression: implications for possible congestive heart failure therapy.

Congestive heart failure (CHF) affects more than five million people in the United States and results in considerable morbidity, mortality, and economic costs. Patients with class III and IV CHF have a 40% to 50% probability of dying 5 years after symptom onset despite optimal therapy, a prognosis worse than many cancers. A variety of drugs and devices have improved survival-the 50% survival time in 1980 was just 18 months-but the outlook for patients remains dismal and the prevalence of CHF continues to increase. This unmet medical need underscores the importance of developing new approaches for the treatment of CHF. This brief review focuses on data from preclinical experiments regarding the effects of increased adenylyl cyclase type 6 (AC6) expression on cellular and cardiac function, and possible mechanisms for the unexpected favorable effects of increased AC6 content on the failing heart.