High blood pressure is a potent trigger for hypertensive heart diseases including cardiac hypertrophy (enlargement of the heart), arrhythmias (cause of sudden cardiac death), and heart failure.  However, the cellular and molecular mechanisms linking hypertension to heart diseases remain unclear.  Our recent studies identify a possible molecular link.  In an animal model for human hypertension and heart disease, we found that the calcium (Ca2+) signal increases just as hypertension develops, long before hypertrophy occurs.  This increase in the Ca2+ signal is important because it can explain how the heart is able to contract more forcefully to maintain cardiac output in the face of increasing blood pressure.  An increase of the Ca2+ signal may also couple into the Ca2+- calmodulin signaling system to affect a variety of downstream signaling pathways including Ca2+-calmodulin dependent protein kinases (CaMKII), calcineurin, and mitogen-activated protein kinases.  Activation of these molecules has been shown to lead to cardiac hypertrophy and heart failure.  Like an increased Ca2+ signal, cardiac hypertrophy serves as a mechanism to maintain cardiac output as blood pressure increases.  We investigate the link between hypertension and remodeling of the Ca2+ signaling system that affect cardiac function and heart disease development.  Our current NIH funded project is to test the potential of using CaMKII inhibitor as a new therapeutic strategy to treat hypertension-induced heart diseases.

This is our first step towards a long-term goal to identify the cellular and molecular mechanisms responsible for the induction of hypertensive heart disease, and to develop new therapies for preventing and mitigating the heart disease development.