2.1.2 Chemical stimuli
A recent study by Ceylan-Isik et al. showed that autophagy-related protein levels of beclin 1, Atg5, Atg7, and LC3-II were observably decreased and hypertrophic markers such as aminopeptidase N (ANP), transcription factor GATA4 and phosphorylated nuclear factor of activated T cells 3 (NFATc3), was activated in H9c2 myoblasts induced by endothelin-1 (ET-1), which is a polypeptide of 21 amino acids [34]. Chen et al. revealed that decreasing of connexin 43, a key protein involved in information transmission among organizations, can attenuate the expression of LC3-II and increase cell death and apoptosis in Ang II-treated H9c2 cells [35]. Another report showed that High-fat diet (HFD) decreased autophagy activity and increased cardiac hypertrophy, fibrosis, and apoptosis [36]. Similar to HFD, Guo et al. found that ethanol can induce the accumulation of acetaldehyde and autophagosomes, then promote cardiac hypertrophy. However, ethanol can also reduce compensatory wall thickening in the hearts of pressure-overloaded (PO) mice [37-39]. These chemical stimuli share a common feature that deteriorates cardiac hypertrophy by altering autophagic levels. Therefore, myocardial hypertrophy can be prevented by targeting these chemical stimuli.