期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 26, 期 8, 页码 2462-2476出版社
WILEY
DOI: 10.1111/jcmm.17275
关键词
apoptosis; cardiac ischaemia; reperfusion injury; ferroptosis; mitochondria; necroptosis
资金
- National Research Council of Thailand
- National Science and Technology Development Agency
- Chiang Mai University
- Thailand Science Research and Innovation
Growing evidence suggests that ferroptosis, apoptosis, and necroptosis contribute to cardiac ischemia/reperfusion injury. This study found that apoptosis and ferroptosis, but not necroptosis, contribute to myocardial damage in acute cardiac ischemia/reperfusion injury. Inhibitors of these pathways provided effective cardioprotection through modulation of mitochondrial function and attenuation of apoptosis and ferroptosis.
Growing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R-operated rats were divided into 4 groups: vehicle, apoptosis (Z-vad), ferroptosis (Fer-1) and necroptosis (Nec-1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z-vad (low and medium doses) or Fer-1 (medium and high doses). Fer-1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec-1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.
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