Oxidative stress and endothelial dysfunction: linking cellular damage to cardiovascular disease and erectile dysfunction

Oxidative stress (OS), the imbalance between reactive oxygen species (ROS) generation and antioxidant defense mechanisms plays a key role in the pathogenesis of endothelial dysfunction, which is a common denominator in cardiovascular disease (CVD) and erectile dysfunction (ED). This review synthesizes current evidence on the molecular mechanisms linking OS to endothelial impairment, emphasizing ROS-induced nitric oxide (NO) depletion, eNOS uncoupling, peroxynitrite formation, and activation of pro-inflammatory signaling. The vascular endothelium, especially in penile arteries due to their small caliber, is highly susceptible to oxidative injury, making ED an early clinical marker of concealed systemic vascular disease. Shared risk factors, such as diabetes, hypertension, obesity, dyslipidemia, and smoking, worsen oxidative damage, leading to a self-generating cycle of inflammation, vasoconstriction, and vascular remodeling that culminates in both CVD and ED. The review explores enzymatic and non-enzymatic antioxidant defenses, sources of vascular ROS (mitochondria, NADPH oxidases, xanthine oxidase), and emerging therapeutic strategies. These include lifestyle modifications (diet, exercise, stress reduction, smoking cessation) and pharmacological interventions (statins, ACE inhibitors, PDE5 inhibitors, mitochondria-targeted antioxidants) that restore NO bioavailability and endothelial function. Early detection and reversal of endothelial dysfunction remain critical for preventing irreversible vascular damage, underscoring the need for integrated diagnostic approaches and personalized management strategies targeting shared redox pathways.