Vascular Aging and Atherosclerosis: The Modulatory Impact of Selenium—A Comprehensive Review

first_pagesettingsOrder Article Reprints This is an early access version, the complete PDF, HTML, and XML versions will be available soon. Open AccessReview Vascular Aging and Atherosclerosis: The Modulatory Impact of Selenium—A Comprehensive Review by Andrea Borghini *ORCID,Mariangela Palazzo andFrancesca Gorini *ORCID Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy * Authors to whom correspondence should be addressed. Cells 2026, 15(11), 973; https://doi.org/10.3390/cells15110973 (registering DOI) Submission received: 27 April 2026 / Revised: 21 May 2026 / Accepted: 21 May 2026 / Published: 25 May 2026 (This article belongs to the Special Issue The Cell Biology of Heart Disease) Downloadkeyboard_arrow_down Review Reports Versions Notes Abstract Selenium (Se), a vital trace element, plays a significant role in maintaining vascular health and may offer protective effects against atherosclerosis. Its actions are mediated through Se-dependent selenoenzymes and selenoproteins, which enhance antioxidant defense, modulate inflammatory responses, and promote autophagy. These processes collectively help prevent cellular senescence—a state associated with age-related vascular decline characterized by oxidative stress, DNA damage, pro-inflammatory activity, and endothelial dysfunction. Epidemiological evidence consistently shows that low Se status is associated with increased risk of atherosclerotic cardiovascular disease within a narrow concentration range. However, clinical trials have not demonstrated clear reductions in cardiovascular events or mortality with Se supplementation alone. Overall, current evidence indicates that Se modulates key mechanisms involved in vascular aging and atherosclerosis, particularly redox balance, immune activation, and vascular cell homeostasis. This comprehensive review summarizes current epidemiological, clinical, and experimental research on the role of Se in cardiovascular health. It underscores Se’s potential as a promising strategy for the prevention and treatment of atherosclerosis, while also acknowledging the complexities and nuances of its effects on vascular health. A deeper understanding of the cellular and molecular mechanisms involved could pave the way for targeted interventions aimed at reducing the burden of atherosclerotic cardiovascular disease.