Lost in translation: miRNAs and mRNAs in ischemic preconditioning and ischemia/reperfusion injury

Abstract

Ischemic stress involves nutrient deprivation, hypoxia, acidosis, and altered levels of various ions and metabolites. Reperfusion, which abruptly alters these parameters, is a second stress to already stressed cells. Ischemic preconditioning, in which brief ischemia alternates with reperfusion to elicit a protective response to ischemia/reperfusion (I/R) injury, revealed the existence of a highly conserved, cell-autonomous, and nearly ubiquitous program. While we often assume that evolutionary selection is irrelevant with respect to myocardial infarctions—which generally occur long after reproduction—the program of ischemia tolerance may date back much further, to hibernating squirrels, turtles, and estivating frogs and snails (extremophiles), which must survive by entering a hypometabolic state. This relationship is further strengthened by the presence of similar signaling pathways and regulatory mechanisms such as mRNA localization and miRNA regulation. These parallels may offer new insights into the myocardial response to I/R injury. This review will explore some of the recent advances in our understanding of autophagy and mitochondrial turnover in the setting of I/R injury, and related findings drawn from research on hibernating extremophiles.

Mesenchymal stem cell conditioned medium alleviates oxidative stress injury induced by hydrogen peroxide via regulating miR143 and its target protein in hepatocytes

“…A growing knowledge of the relation between aberrant miRNA expression and hepatocyte injury [ 22 , 23 ]. Studies suggest that MSC-CM possesses the capacity to change the expression of miRNA, leading to alteration in the cell microenvironment, and play a prominent role in cell repair [ 17 ].…”

Rapamycin Treatment Reduces Acute Myocarditis Induced by <b><i>Trypanosoma cruzi</i></b> Infection

“…This drug is a classical autophagic inducer and a clinically used immunosuppressive drug that impairs lymphocyte proliferation [9,10] and reduces organ rejection in cardiac and renal-transplanted patients [11], for example. Several mTORC1 blockers are available for patients' treatments, but this therapeutic alternative must be carefully planned [12], as primary biological pathways can be affected directly or indirectly, as the reduction of inflammatory responses and cell death. In the case of experimental models using rapamycin, it leads to increased longevity and can improve cardiac function in different pathologies [13].…”

Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury

“…By contrast, BAG3 knockdown significantly reduced autophagy flux, leading to the accumulation of damaged mitochondria and an increase in apoptosis (12). It is well known that mitochondrial dysfunction and damage are central to the pathophysiology of ischemia/reperfusion (I/R) injury, as the inability to eliminate damaged mitochondria leads to increased production of ROS and, ultimately, to cell death (13,14). Therefore, we hypothesized that BAG3 might play a role in I/R injury.…”