Alterations in the Eicosanoid Profile and Mitochondrial Injury in Human Ventricular Tissue Following Myocardial Infarction

Abstract

Study objectiveMyocardial infarction (MI) accounts for a significant proportion of death and disability in the ageing population. n‐6 PUFAs linoleic acid and arachidonic acid have come under investigation for their role in mediating a cardiac response following ischemic injury. CYP450 metabolism of these fatty acids results in formation of numerous metabolites, called eicosanoids, which can be further metabolised by the enzyme soluble epoxide hydrolase (sEH). These lipid mediators exhibit a wide range of cellular effects including alterations to mitochondria structure and function which may impact cardiac performance. This study investigated alterations to CYP‐derived eicosanoids and mitochondria in heart tissue obtained from individuals who experienced a previous MI.MethodsSamples were obtained from male and female individuals included in the Human Explanted Heart Program and correlated to non‐failing control hearts (NFC) collected from unused transplant donors through the Human Organ Procurement and Exchange Program at the University of Alberta. Ventricular tissues were harvested from patients who had previously experienced a LAD infarct (≥2yrs), as determined by echocardiography, ECG and coronary angiograms. Protein expression was determined by immunoblotting techniques. Mitochondrial enzymatic activities were assessed by spectrophotometric methods while mitochondrial ultrastructure and cristae density were assessed by electron microscopy. A metabolic profile in ventricular tissue was obtained by LCMS.ResultsMarked differences in both LA and AA metabolic profiles were revealed in post‐MI tissues. There were significant increases in cardiotoxic metabolites correlating with decreased cardiac function and injury. Interestingly, there was a significant increase in both sEH activity and expression in post‐MI tissues compared to NFC. Expression of mitochondrial proteins remained unchanged, however enzymatic function declined in post‐MI tissues compared to NFC correlating with marked disruption in mitochondrial ultrastructure.ConclusionsThese data provide the first evidence demonstrating a marked shift in eicosanoid metabolism in post‐MI hearts that correlates with mitochondrial structural disruption and overall decreased mitochondrial function.Support or Funding InformationSupport for this project was provided by the Canadian Institutes of Health Research.KL Jamieson is supported by funding from Alberta Innovates‐Health Solutions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.