Abstract
Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events across diverse cardiac cell types. In cardiomyocytes, ROS overload impairs contractility and survival, contributing to heart failure and infarction. Cardiac fibroblasts respond by promoting fibrosis through excessive collagen deposition. Macrophages intensify inflammatory responses, such as atherosclerosis, via ROS-mediated lipid oxidation-acting both as mediators of damage and targets for antioxidant intervention. This review examines how oxidative stress affects cardiac cell types and evaluates antioxidant-based therapeutic strategies. Therapeutic approaches include natural antioxidants (e.g., polyphenols and vitamins) and synthetic agents (e.g., enzyme modulators), which show promise in experimental models by improving myocardial remodeling. However, clinical trials reveal inconsistent outcomes, underscoring translational challenges (e.g., clinical biomarkers). Emerging strategies-such as targeted antioxidant delivery, activation of endogenous pathways, and disease modeling using 3D organoids-aim to enhance efficacy. In conclusion, we spotlight innovative technologies-like lab-grown heart tissue models-that help scientists better understand how oxidative stress affects heart health. These tools are bridging the gap between early-stage research and personalized medicine, opening new possibilities for diagnosing and treating heart disease more effectively.