Upregulation of Nrf2 in myocardial infarction and ischemia-reperfusion injury of the heart.
Sahar ZuberiHira RafiAzhar HussainSatwat HashmiPublished in: PloS one (2024)
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. During reperfusion, reactive oxygen species are released and this causes further insult to the myocardium, resulting in ischemia-reperfusion (IR) injury. Since Nrf2 is a key regulator of redox balance, it is essential to determine its contribution to these two disease processes. Conventionally Nrf2 levels have been shown to rise immediately after ischemia and reperfusion but its contribution to disease process a week after the injury remains uncertain. Mice were divided into MI, IR injury, and sham surgery groups and were sacrificed 1 week after surgery. Infarct was visualized using H&E and trichrome staining and expression of Nrf2 was assessed using immunohistochemistry, Western blot, and ELISA. MI displayed a higher infarct size than the IR group (MI: 31.02 ± 1.45%, IR: 13.03 ± 2.57%; p < 0.01). We observed a significantly higher expression of Nrf2 in the MI group compared to the IR model using immunohistochemistry, spot densitometry of Western blot (MI: 2.22 ± 0.16, IR: 1.81 ± 0.10, Sham: 1.52 ± 0.13; p = 0.001) and ELISA (MI: 80.78 ± 27.08, IR: 31.97 ± 4.35; p < 0.01). There is a significantly higher expression of Nrf2 in MI compared to the IR injury group. Modulation of Nrf2 could be a potential target for therapeutics in the future, and its role in cardioprotection can be further investigated.
Keyphrases
- oxidative stress
- poor prognosis
- ischemia reperfusion injury
- acute myocardial infarction
- heart failure
- reactive oxygen species
- south africa
- left ventricular
- randomized controlled trial
- clinical trial
- cell proliferation
- metabolic syndrome
- type diabetes
- small molecule
- adipose tissue
- transcription factor
- atrial fibrillation
- climate change
- insulin resistance
- high resolution
- mass spectrometry
- double blind
- blood brain barrier
- current status