2. Roles of autophagy in cardiac hypertrophy
Pathological cardiac hypertrophy is one of the pathological
manifestations of cardiovascular disease remains the world’s leading
cause of death. Cardiomyocyte autophagy plays complicated but
indispensable roles in helping preserve normal metabolism and function
of the heart. Importantly, pieces of evidence have revealed that
autophagy plays a critical role in cardiac hypertrophy (Fig. 2). On the
one hand, autophagy can act as a pro-survival factor in cardiac
hypertrophy. Firstly, autophagy can promote the degradation of aging and
damaged organelles, long-lived proteins and misfolded proteins to supply
part of the energy needed by the heart. Secondly, some growth hormones
such as insulin and IGF-1 (insulin-like growth factor 1), which are the
upstream regulator of autophagy, can promote physiological cardiac
hypertrophy development [26]. For example, Mcmullen et al.have reported that growth hormones (e.g., insulin) and activated several
signaling pathways such as PI3K (phosphoinositide 3-kinase), Akt
(protein kinase B), AMPK (AMP-activated protein kinase), and mTOR
(mechanistic target of rapamycin), also participate in autophagy pathway
[26-28]. Thirdly, autophagy eliminates the ill effects of ROS on
cardiomyocytes by removing damaged mitochondria from hypertrophic
hearts. On the other hand, autophagy can act as a pro-death factor in
cardiac hypertrophy. For instance, Nakai and Taneike et al. found
that conditional inactivation of either the Atg5 or Atg7genes in the adult heart, which led to abrogation of autophagy pathways,
resulted in rapid onset of cardiac hypertrophy, left ventricular
dilation, and diminished cardiac output [25, 29]. Therefore, under
physiological conditions, basal autophagy maintains cell metabolic
balance by transforming damaged organelles into energy substances (e.g.,
amino acids) and controlling protein quality, and promotes myocardial
survival [30]. However, Qi et al. reported that autophagy
flux is markedly induced in a swimming- induced and IGF-1-induced
physiological cardiac hypertrophy rat model, which indicated that
excessive autophagy was also occurred during cardiac hypertrophy and
might be harmful [28, 30, 31].