Therapeutic Strategies for Endothelial Dysfunction in Cardiovascular Disease, Rheumatoid Arthritis, and Diabetes: Current and Emerging Approaches.

Abstract

The endothelium forms the inner vital lining of blood vessels and controls vascular tone, hemostasis, and inflammation, maintaining cardiovascular homeostasis. Endothelial dysfunction, characterized by abnormal vasodilation, increased oxidative stress, and decreased nitric oxide bioavailability, is a key pathophysiological mechanism underlying many cardiovascular diseases. The review examines current approaches for addressing endothelial dysfunction in various disease states, with a special emphasis on cardiovascular disease, rheumatoid arthritis, and diabetes mellitus. We performed a thorough review of the literature on studies that investigated interventions for endothelial dysfunction in cardiovascular diseases, rheumatoid arthritis, and diabetes mellitus. Mechanisms of action, clinical effectiveness, and novel strategies were the primary focus of data extraction. Well-established therapies such as statins, ACE inhibitors, and antihypertensive drugs show robust benefits in enhancing endothelial function through antiinflammatory, antioxidant, and vasodilatory actions. Novel therapies targeting molecular pathways such as the NLRP3 inflammasome, YAP/TAZ signaling, and microRNA modulation have shown promising results in preclinical and early-stage clinical trials. Emerging drugs such as resveratrol, astragaloside IV, and SGLT-2 inhibitors also demonstrate favorable effects on endothelial function via various mechanisms. Non-pharmacological lifestyle interventions, including exercise and caloric restriction, provide complementary benefits, especially when used alongside pharmacotherapy. Endothelial dysfunction is a critical modifiable target in many disease states. Although traditional cardiovascular medications remain the cornerstone of treatment, novel targeted therapies and combination strategies are promising approaches to enhance endothelial function and reduce cardiovascular morbidity and mortality. Personalized treatments based on individual patients' specific pathophysiological mechanisms underlying their endothelial dysfunction should be the research focus in the future.