Intracardiac administration of ephrinA1-Fc preserves mitochondrial bioenergetics during acute ischemia/reperfusion injury

Publication date: Available online 13 November 2019Source: Life SciencesAuthor(s): Maria J. Torres, Kelsey L. McLaughlin, Randall H. Renegar, Smrithi Valsaraj, K’Shylah S. Whitehurst, Omar M. Sharaf, Uma M. Sharma, Julie L. Horton, Brinda Sarathy, Justin C. Parks, Jeffrey J. Brault, Kelsey H. Fisher-Wellman, P. Darrell Neufer, Jitka A.I. ViragAbstractAimsIntracardiac injection of recombinant EphrinA1-Fc immediately following coronary artery ligation in mice reduces infarct size in both reperfused and non-reperfused myocardium, but the cellular alterations behind this phenomenon remain unknown.Main methodsHerein, 10 wk-old B6129SF2/J male mice were exposed to acute ischemia/reperfusion (30minI/24hrsR) injury immediately followed by intracardiac injection of either EphrinA1-Fc or IgG-Fc. After 24 hrs of reperfusion, sections of the infarct margin in the left ventricle were imaged via transmission electron microscopy, and mitochondrial function was assessed in both permeabilized fibers and isolated mitochondria, to examine mitochondrial structure, function, and energetics in the early stages of repair.Key findingsAt a structural level, EphrinA1-Fc administration prevented the I/R-induced loss of sarcomere alignment and mitochondrial organization along the Z disks, as well as disorganization of the cristae and loss of inter-mitochondrial junctions. With respect to bioenergetics, loss of respiratory function induced by I/R was prevented by EphrinA1-Fc. Preservation of cardiac bi...
Source: Life Sciences - Category: Biology Source Type: research