The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

Figure 3

This scheme depicts the role of ROS in the pathophysiology of diabetic cardiomyopathy and myocardial ischemia/reperfusion injury. ROS triggers the activation of MAPKs in the cardiomyocytes, which results in the activation of transcription factors such as NFκB, AP-1. This results in the expression of proinflammatory cytokines and prohypertrophy proteins. Further, ROS directly induces DNA damage and activates poly (ADP-ribose) polymerase (PARP-1) in the nucleus, whereby it mends the damaged DNA. Overactivation of PARP-1 results in depletion of ATP, MPTP opening, mitochondrial dysfunction, and initiation of apoptotic cell death pathways. Next, ROS depletes NO^• in the cardiac microvasculatures and promotes endothelial dysfunction via ONOO⁻ generation. Further ROS induces myocardial fibrosis via activation of profibrotic mediators such as TGFβ and priming the epithelial mesenchymal transition (EMT) process of cardiac fibroblasts (CF) differentiation to myofibroblasts (MF), which produces the extracellular matrix. In addition, ROS also perturbs the calcium handling capacity of the cardiomyocytes and interferes in the autophagy process. All these phenotypic events modulated by ROS orchestrates in the development of cardiac failure. Collagen-1 (Coll-1); connective tissue growth factor (CTGF); cyclic GMP (cGMP); protein kinase G (PKG).