2.1.1 Abnormal expression of autophagy-related genes
Autophagy-related genes play a crucial role in the initiation and elongation of the autophagosome and also participate in the fusion of autophagosome and lysosome to form autolysosome. Accordingly, abnormal expression of Atgs may be an important factor affecting pathological cardiac hypertrophy. Recently, Ljubojević-Holzer et al . found that loss of cardiac Atg5 can reduce mitochondrial abundance and disrupt Ca2+ cycling and eventually lead to energetic exhaustion and myocardial damage [32]. Nakai et al . found that cardiac-specific autophagy-related 5 (Atg5 )-deficient mice developed left ventricular dilation, contractile disorders, and a significant increase in a myocardial cross-sectional area [25]. Another animal model autophagy-related 7 (Atg7 )-knockdown rat phenocopied the effects of Atg5 deficiency [25]. Results also showed that protein levels of microtubule-associated protein 1 light chain 3-II (LC3-II) were significantly decreased with cardiomyocyte hypertrophy. Cao et al . found that overexpression of beclin 1, which is indispensable for autophagosome formation, promoted autophagy induction and hypertrophic, maladaptive growth of cardiac muscle [33]. These studies provided direct evidence that the abnormal expression of core autophagy factors is indeed a contributing factor to promote cardiac hypertrophy.