A PKGarious Balancing Act

The pathologically hypertrophied and failing heart is a battlefield in a war that would make even George Lucas proud. On the one side, you have hemodynamic, neurohormonal, morphological, and cellular/molecular dark forces urging the ventricle toward decompensation and ultimate demise. On the other, Jedi signaling cascades try valiantly to stave off the impending disaster. Alas, unlike the movies, the dark side often wins, and we need better-equipped counterforces to change this. Current heart failure therapies are fairly defensive—blocking neurohumoral stimuli and hemodynamic overload. However, adaptive/offensive strategies are advancing, including those aimed at enhancing metabolism, vascular supply, and cell regeneration, and those activating molecular signaling to counter maladaptation.