ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using…

• NN
  National Natural Science Foundation of China

  Awards: 2017YFC1700400, U1801284, 81904068, 81903821, 81873209, 82125038, 2017BT01Y036
• NS
  Natural Science Foundation of Guangdong Province

  Awards: 2021A1515011297, 2019A1515010909
• KC
  K. C. Wong Education Foundation
• GP
  Guangdong Provincial Pearl River Talents Program

  Award: 2017BT01Y036
• NK
  National Key Research and Development Program of China

  Awards: 2022YFC0867400, 2017YFC1700404, 2017YFC1700400