Myocyte hypertrophy and apoptosis: a balancing act

Abstract

In response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress the heart responds by enlarging the individual myofibers. Even though myocardial hypertrophy can normalize wall tension, it instigates an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure, suggesting that in most instances hypertrophy is a maladaptive process. Increasing evidence suggests that several of the signaling cascades controlling myocyte growth in the adult heart also function to enhance survival of the myocyte population in response to pleiotropic death stimuli. In this review, we summarize recent insights into hypertrophic signaling pathways and their ability to control the balance between myocyte life and death. As modulation of myocardial growth by antagonizing intracellular signaling pathways is increasingly recognized as a potentially auspicious approach to prevent and treat heart failure, the design of such therapies should respect the dichotomous action of pathways that dictate a balance between myocyte hypertrophy, survival and death.

iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death

“…Neonatal cardiomyocytes do not form proper intercalated disc structures until day 15 of mouse postnatal development (41). Additionally, the establishment of survival signals during hemodynamic changes or cardiac injuries is required to protect nonproliferative, fully differentiated cardiomyocytes (42). Therefore, in embryonic cardiomyocytes in which intercalated discs are not formed or in adult hearts subjected to stress conditions, iASPP may locate at the cytoplasm or even in the nucleus, instead of at cell-cell junctions where it can interact with p53 and p63 to prevent apoptosis (43)(44)(45).…”

A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload

“…When subject to one of these negative stimuli, the heart undergoes concentric remodelling in order to normalize (1) and worldwide (9). As well, it is the most common cause of morbidity and mortality in industrialized countries (10).…”

Morphological and molecular changes of the myocardium after left ventricular mechanical support

“…In response to an increased workload, individual cardiomyocytes react by adaptive hypertrophic growth, i.e. they increase in cell size, volume and mass, or undergo apoptosis, respectively [23,24]. As a result, there is organ enlargement, cardiac dilation and increased sphericity [22].…”

“…As a result, there is organ enlargement, cardiac dilation and increased sphericity [22]. Although salutary at the beginning by reducing wall tension, hypertrophy eventually becomes a maladaptive process, leading to chronic heart failure (CHF) and cardiac mortality [23,24]. Dilation is followed by increased ventricular wall stress resulting in decreased coronary blood flow, impaired pump function and diminished cardiac output [25].…”