Molecular Insights into Oxidative-Stress-Mediated Cardiomyopathy and Potential Therapeutic Strategies

Figures

• 

  Figure 1. Pathogenic Mechanisms of ROS in Cardiomyopathies. ROS, including superoxide (O2⁻), hydrogen peroxide (H2O2), and hydroxyl radicals (OH·), originate primarily from mitochondria and NADPH oxidases (NOX), particularly NOX2. Excessive ROS production damages proteins, lipids, and DNA, impairing mitochondrial function and activating NF-κB signaling, which promotes inflammation, increases mitochondrial membrane permeability, and triggers apoptosis via cytochrome c release and caspase activation. In diabetic cardiomyopathy, hyperglycemia-induced ROS generation via the AGE-RAGE pathway exacerbates OS. Stress-induced cardiomyopathy is driven by excessive catecholamine release, while doxorubicin-induced cardiomyopathy involves ROS overproduction through NOS and NOX dysfunction. In septic cardiomyopathy, impaired mitochondrial electron transport amplifies ROS generation. This persistent oxidative damage creates a vicious cycle of mitochondrial dysfunction, accelerating cardiomyopathy progression.

• 

  Figure 2. Pathophysiological Mechanisms of DCM. Hyperglycemia, ROS, dyslipidemia, advanced glycation end products, and alterations in the RAAS are primary contributors to the development of DCM. These factors disrupt calcium ion transport, leading to calcium homeostasis imbalance and mitochondrial dysfunction, both of which contribute to cardiotoxicity. Concurrently, impaired insulin signaling and dysregulated free fatty acid metabolism result in lipid accumulation, further exacerbating the pathological changes. Together, these mechanisms promote myocardial inflammation, fibrosis, apoptosis, contractile dysfunction, and microvascular obstruction, culminating in the clinical manifestation of DCM.