Although the existence of a balance between cardiomyocyte apoptotic death and regeneration has been denied, recent observations have been made showing that exaggerated cardiomyocyte apoptosis occurs in diverse conditions. One of these conditions is hypertensive heart disease (HHD) in which complex changes in myocardial composition develop that are responsible for the structural remodeling and dysfunction of the myocardium. One of these changes is a diminished number of cardiomyocytes due to enhanced apoptotic cell death. In fact, cardiomyocyte apoptosis has been shown to be abnormally stimulated in patients with HHD, namely those with heart failure. Cardiomyocyte apoptosis has been proposed to occur as a result of an imbalance among the extracellular factors that induce apoptosis (pressure overload and neuro-humoral activation) and those factors that act within the cell determining its resistance or susceptibility to apoptosis (i.e., survival pathways)). In this regard, the transmembrane signal transducer glycoprotein (gp)130 has been proposed to exert a survival effect in cardiomyocytes, mediating apoptosis-supressor signals triggered by members of the interleukin-6 cytokine family, including cardiotrophin-1. Specific left ventricular gp130 knockout mice develop a rapid dilated cardiomyopathy with massive cardiomyocyte apoptosis in response to mechanical overload. Interestingly, an association of diminished expression of either gp130 or LIF proteins with increased cardiomyocyte apoptosis has been found in the hypertrophied heart of hypertensive patients and SHR. It thus can be hypothesized that inhibition of the gp130 signaling pathway in HHD decreases the survival capability of cardiomyocytes and makes them more susceptible to apoptotic factors.