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.