Molecular mechanisms of autophagy in cardiac ischemia/reperfusion injury (Review)

Abstract

Autophagy is a maintenance process for recycling long-lived proteins and cytoplasmic organelles. The level of this process is enhanced during ischemia/reperfusion (I/R) injury. Autophagy can trigger survival signaling in myocardial ischemia, whereas defective autophagy during reperfusion is detrimental. Autophagy can be regulated through multiple signaling pathways in I/R, including Beclin‑1/class III phosphatidylinositol‑3 kinase (PI‑3K), adenosine monophosphate activated protein kinase/mammalian target of rapamycin (mTOR), and PI‑3K/protein kinase B/mTOR pathways, which consequently lead to different functions. Thus, autophagy has both protective and detrimental functions, which are determined by different signaling pathways and conditions. Targeting the activation of autophagy can be a promising new therapeutic strategy for treating cardiovascular disease.

Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways

“…Human cardiomyocyte ventricular primary cells (Celprogen, Torrance, CA, USA) were cultured following the recommended manufacturer's protocols in extracellular matrix pre-coated flasks and/or well plates with ready-to-use complete growth medium (Celprogen, Torrance, CA, USA ). The choice of such human cell lines was guided by previous evidence showing their high reliability for evaluating oxidative stress, antioxidant signaling pathways and IR injuries [19,27,28]. Human hepatocarcinoma HepG2 cells (Sigma-Aldrich, St. Louis, MI, USA) were cultured in EMEM medium (Invitrogen, Carlsbad, CA, USA) and used as control cells to test the presence of NPC1L1 receptor.…”

Effects of intermittent hypoxia on the cell survival and inflammatory responses in the intertidal marine bivalves Mytilus edulis and Crassostrea gigas

“…Studies in model organisms, such as terrestrial mammals, Drosophila and Caenorhabditis elegans highlight the important role of autophagy and apoptosis in the cellular response to H-R, which may be beneficial or detrimental depending on the intracellular conditions and the extent of autophagy and apoptosis (Ham and Raju, 2016;Lin et al, 2018;Sciarretta et al, 2011;Zhou et al, 2017). Autophagy is a catabolic process involved in recycling of long-lived proteins and organelles in the cell during normal cell maintenance (Bialik et al, 2018).…”

“…Autophagy is a catabolic process involved in recycling of long-lived proteins and organelles in the cell during normal cell maintenance (Bialik et al, 2018). Under hypoxic conditions, when the cells experience energy and nutrient deficiency, the autophagic processes are activated, providing substrates for anaerobic ATP production and removing superfluous or damaged intracellular structures (Lin et al, 2018;Solaini et al, 2010). However, during reoxygenation, oxidative stress, calcium overload and mitochondrial dysfunction lead to a major increase of autophagy which may result in tissue injury in hypoxia-sensitive organisms such as terrestrial mammals (Ham and Raju, 2016;Lin et al, 2018;Sciarretta et al, 2011).…”

Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury via Suppressing NLRP3 Inflammasome and Activating Autophagy

“…Moreover, AMPK is known as the upstream of mTOR which play an important role in the regulation of inflammation and autophagy. However, autophagy is a complex dynamic process, and multiple signaling pathways are considered to trigger autophagy in MI/R, including Beclin-1/class III phosphatidylinositol-3 kinase (PI3K), AMPK/mTOR, and PI-3K/Akt/mTOR pathways ( Wang et al, 2015 ; Lin et al, 2018 ). Whether HSYA regulates autophagy through other signaling pathways requires further experimental investigation.…”