Role of Nrf2 in myocardial infarction and ischemia-reperfusion injury

Abstract

Background: Myocardial infarction (MI) is a leading cause of morbidity and mortality in the world and is characterized by ischemic necrosis of an area of the myocardium permanently devoid of blood supply. With advancements in therapeutics, thrombolytic agents and primary percutaneous coronary intervention (PCI) can now be employed to reperfuse the ischemic area. Reperfusion, in itself generates reactive oxygen species and this causes further insult to the myocardium, thereby resulting in ischemia-reperfusion (IR) injury. Since Nrf2 is a key regulator of redox balance, it essential to determine its contribution in these two disease processes. Conventionally Nrf2 levels have been shown to rise immediately after ischemia and reperfusion but its contribution to disease process in the days that follow remains uncertain. Objective: This study intended to demonstrate the difference in Nrf2 levels one week after myocardial infarction and ischemia-reperfusion injury, respectively. Methods: Mice were divided into MI, IR injury and sham surgery group and were sacrificed 1 week after surgery. In MI model, left anterior descending artery was ligated permanently while in IR model, it was temporarily ligated for 30mins and reperfused. Infarct size was estimated using trichrome staining and expression of Nrf2 was assessed using immunohistochemistry, Western blot and ELISA. Results: Infarct size was the highest in MI group, followed by IR (MI: 31.02 ± 1.45%, IR: 13.03 ± 2.57%; p < 0.01). We observed a significantly higher expression of Nrf2 in MI group compared to IR model using immunohistochemistry, spot densitometry of Western blot (MI: 2.13 ± 0.22, IR: 1.69 ± 0.25; p = 0.039) and ELISA (MI: 80.78 ± 27.08, IR: 31.97 ± 4.35; p < 0.01). Conclusion: There is a significantly higher expression of Nrf2 in MI compared to IR injury group. Modulation of Nrf2 could be a potential target for therapeutics in the future, and its role in cardiprotection can be further investigated. Aga Khan University University Research Council Funding This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.