Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia/reperfusion injury.

Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia/reperfusion injury. Am J Physiol Heart Circ Physiol. 2021 Jan 29;: Authors: Stamenkovic A, O'Hara KA, Nelson DC, Maddaford TG, Edel AL, Maddaford G, Dibrov E, Aghanoori M, Kirshenbaum LA, Fernyhough P, Aliani M, Pierce GN, Ravandi A Abstract Myocardial ischemia/reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs) which results in cell death. However, the mechanism by which OxPCs mediate cell death is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Cardiomyocyte viability, bioenergetic response and calcium transients were determined in the presence of OxPCs. Fragmented OxPCs resulted in a decrease in cell viability with POVPC and PONPC having the most potent cardiotoxic effect in both a concentration and time dependent manner (P<0.05). POVPC and PONPC also caused a significant decrease in Ca2+ transients and net contraction in isolated cardiomyocytes compared to vehicle treated control cells (P<0.05). PONPC depressed maximal respiration rate (p<0.01; 54%) and spare respiratory capacity (p<0.01; 54.5%). Notably, neither caspase 3 activation or TUNEL staining was observed in cells treated with either POVPC or PONPC. Further, cardiac myocytes treated with OxPCs were indistinguishable from vehicle treated contr...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research