Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Figure 2

The damage of oxidative stress to cardiomyocytes during reperfusion. Reactive oxygen species affect Ca²⁺ overload and Bcl-2 family proteins, which lead to the mitochondrial permeability transformation pore opening and ultimately lead to myocardial apoptosis. Reactive oxygen species also trigger exogenous apoptosis by activating the MAPK family. Finally, reactive oxygen species initiate apoptosis through ER stress. Beclin1 and LAMP2, which are regulated by reactive oxygen species, cause impaired autophagy or excessive autophagy, thereby damaging cardiomyocytes. Via inflammatory response, reactive oxygen species induce pathological damage of the heart. NO, one of the members of reactive nitrogen, damages cardiomyocytes through direct cytotoxicity or generates ONOO^- with O₂⁻ to cause cardiomyocyte damage. Abbreviations: MAPK: mitogen-activated protein kinase; NF-κB: nuclear transcription factor-κB; TNF-α: tumor necrosis factor-α; TNFR1: tumor necrosis factor receptor 1; Fas: tumor necrosis factor superfamily; CyP-D: cyclophilin D; Bcl-2: B cell lymphoma-2; MPTP: mitochondrial permeability transition pore; AIF: apoptosis-inducing factor; Cyt: cytochrome; LAMP2: lysosomal-associated membrane protein 2; Apaf-1: apoptosis protease-activating factor-1; ONOO^-: peroxynitrite; NLRP3: nucleotide-binding oligomerization domain-like receptor protein 3; MMPs: matrix metalloproteinases; ER stress: endoplasmic reticulum stress; CHOP: CCAAT/enhancer-binding protein homologous protein.