Isorhapontigenin, A New Resveratrol Analog, Attenuates Cardiac Hypertrophy Via Blocking Signaling Transduction Pathways

Isorhapontigenin, a new resveratrol analog, attenuates cardiachypertrophy via blocking signaling transduction pathways Cardiomyocyte hypertrophy is the cellular response to an increase in biomechanical stress, including extrinsic, such as in arterial hypertension or valvular heart disease, or intrinsic, as in familial hypertrophic cardiomyopathy. The defining features of hypertrophy are an increase in cardiomyocyte size, enhanced protein synthesis, and a higher organization of the sarcomere. These changes in cellular phenotype are preceded and accompanied by the reinduction of the so-called fetal gene program. Although hypertrophy in response to pathologic signaling has traditionally been considered an adaptive response required to sustain cardiac output in the face of stress, prolonged hypertrophy is associated with a significant increase in the risk for sudden death or progression to heart failure, independent of the underlying cause of hypertrophy. The major bioactive peptide of the rennin-angiotensin system, angiotensin II (Ang II), plays a fundamental role not only in hypertrophy but also in various cardiovascular diseases such as hypertension, atherosclerosis, hypertrophy, and heart failure. Accumulating in vitro and in vivo evidence demonstrated that the effects of Ang II on cardiac intracellular signaling cascades are essential to elucidate the molecular mechanism underlying Ang II induced pathological cardiac hypertrophy. The signal transduction pathways of cardiac hypertrophy have attracted a great deal of attention because of the potential to develop novel pharmacological interventions against heart failure by targeting early signaling events of cardiac myocyte hypertrophy. Several intracellular signaling pathways play important roles in developing cardiac hypertrophy, including the PKC pathway, the MAPK cascades pathway, the PI3K pathway, and the NF-kB and AP-1 pathways. Cardiac hypertrophy is the consequence of hypertrophic stimulus induced changes in gene expression, which is linked by intracellular signal transduction. It is likely, however, that there are "molecular phenotypic" differences underlying cardiac hypertrophy triggered by different stimuli, which is caused by the different signal pathways that they initiated.