Unraveling the complexities of cardiac remodeling and hypertrophy - High-content screening and computational modeling

摘要

Heart weight directly correlates with body weight in most mammals under homeostatic conditions [1 ]. However, numerous stimuli and stresses have been found to elicit myocardial growth, increase heart size, and remodel ventricular shape. Physiological provocations, such as pregnancy and exercise, result in an increase in heart size accompanied by enhanced cardiac output that is completely reversible and not related to adverse events later in life. On the other hand, it has been appreciated for some time that numerous molecular signals elicit hypertrophy and remodeling that initially could be considered a positive response to cope with an acute insult, but with persistent signaling become maladaptive. Numerous stressors have been implicated in pathological cardiac hypertrophy/ remodeling including: aortic valve stenosis, severe mitral valve regurgita-tion, genetic mutations, hypertension and myocardial infarction, where the remote myocardium must compensate for the lost region of cardiomyocytes [2].