Abstract
Atherosclerosis-induced erectile dysfunction (AED) is a common and clinically significant vascular disorder that affects men's quality of life and serves as a potential early indicator of systemic cardiovascular disease (CVD). Atherosclerosis (AS), characterized by arterial wall inflammation, lipid accumulation, and endothelial damage, shares critical risk factors with AED, including hypertension, diabetes, hyperlipidemia, and smoking. These shared pathogenic drivers contribute to a bidirectional relationship: AS accelerates erectile dysfunction (ED) through vascular impairment, while ED often precedes overt cardiovascular events, highlighting its role as a "window" into systemic vascular health. Despite the widespread use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy, their efficacy is limited in severe cases due to persistent endothelial dysfunction, underscoring the need to clarify the vascular endothelial mechanisms underlying AED for optimized therapeutic strategies. This review systematically analyzes the role of vascular endothelial mechanisms in AED progression through a comprehensive literature synthesis. Key focuses include pathophysiological interactions between endothelial dysfunction and cavernosal hypoxia, molecular biomarkers linking AS to erectile impairment, and clinical evidence from trials evaluating endothelial-targeted therapies. Mechanistically, the decreased activity of endothelial nitric oxide synthase (eNOS)-a critical enzyme in nitric oxide (NO) production-is strongly associated with increased AED severity. Reduced NO bioavailability impairs cavernosal smooth muscle relaxation, while endothelial damage triggers inflammatory cascades, oxidative stress, and transforming growth factor-β (TGF-β)-mediated fibrosis, further exacerbating ED. Clinically, this review highlights that combining PDE5 inhibitors with endothelial repair agents (e.g., statins or anti-inflammatory therapies) enhances therapeutic effects by restoring NO signaling and mitigating vascular damage. Additionally, emerging strategies such as nanomedicine-targeted drug delivery and gene therapy show promise in protecting endothelial integrity. Collectively, these findings confirm that vascular endothelial dysfunction serves as both a key biomarker and actionable therapeutic target in AED management. Multimodal therapies addressing endothelial health not only improve erectile function but also hold potential for reducing systemic atherosclerotic risk, emphasizing a holistic approach to AED care.