Roles of autophagy in sepsis-induced myocardial dysfunction: a comprehensive review

Sepsis-induced myocardial dysfunction (SIMD) is a worldwide health issue. Regarding malignant cardiac dysfunction and mortality, the fatality rate of SIMD accounts for 70-90%. The molecular mechanisms that underlie the inflammatory effects and cardiac function of SIMD appear to be intricate. A crucial cellular process associated with cardiomyopathy is the death of cardiomyocytes. In the review, we have summarized the present evidence on the role of autophagy in the pathomechanism of SIMD. The included studies suggest that cardiomyocyte death induced by SIMD might be partially regulated by autophagy and its associated genes and pathways, including but not limited to Unc-51 like-autophagy-activating kinase 1 (ULK1), Zinc finger antisense 1 (ZFAS1), miR-590-3p, miR-214-3p, miR-21-3p, Silent information regulator 1 (SIRT1), SH3 domain-containing protein 2 (SORBS2), AMP-activated protein kinase (AMPK), Mammalian target of rapamycin (mTOR), TLR4/ERK1/2/NF-κB, TFEB-CLEAR, and Tensin homolog deleted on chromosome 10/Protein kinase B (PTEN/AKT) pathway. The crosstalk among autophagy and its associated genes it might be one of the pivotal molecular and cellular mechanisms for SIMD. In addition, some interventions for treating SIMD, e.g. exogenous fibroblast growth factor 21, melatonin, urolithin A, and minocycline, were reported to be associated with their effects on the regulation of autophagy. However, due to limited research, the potential molecular mechanism underlying autophagy in regulating SIMD is unclear and requires further exploration through in vitro and in vivo experiments. Overall, a deeper understanding of SIMD pathogenesis may facilitate new prospects of therapeutic applications targeted to autophagy.