UCLA

Cardiac hypertrophy, defined as an enlargement of the ventricles, is often triggered when the heart is subjected to hemodynamic stress from physiological stimuli such as pregnancy, or from pathological stimuli such as pressure overload-induced left ventricular hypertrophy or pulmonary hypertension-induced right ventricular hypertrophy. Physiological hypertrophy is beneficial and adaptive, while pathological hypertrophy is maladaptive and detrimental.

Estrogen treatment prior to the onset of pathological stimuli is known to attenuate the progression of the onset of ventricular hypertrophy, cardiac dysfunction and subsequent failure. However it was not known whether estrogen is also effective in rescuing heart failure since heart failure is not often diagnosed early and therapeutic intervention after the onset of hypertrophy and failure is necessary. In Chapters 3 and 4 I use two different models of hypertrophy and failure, the pressure overload-induced left ventricular hypertrophy and failure as well as the pulmonary hypertension-induced right ventricular hypertrophy and failure. I show that short-term estrogen therapy after the onset of cardiac dysfunction in both models rescues function via activation of the estrogen receptor β. This rescue action of estrogen is also associated with reversal of cardiac fibrosis and stimulation of angiogenesis, both of which are essential in nurturing the heart.