Exploring endothelial dysfunction in major rheumatic diseases: current trends and future directions

J Mol Med (Berl). 2025 Jun;103(6):635-649. doi: 10.1007/s00109-025-02539-8. Epub 2025 Apr 14.

Abstract

The relationship between rheumatic diseases (RDs) and endothelial dysfunction (ED) is intricate and multifaceted, with chronic inflammation and immune system dysregulation playing key roles. RDs, including Osteoarthritis (OA), Rheumatoid arthritis (RA), Systemic Lupus erythematosus (SLE), Ankylosing spondylitis (AS), Psoriatic arthritis (PsA), Sjogren's syndrome (SS), Systemic sclerosis (SSc), Polymyalgia rheumatica (PMR) are characterized by chronic inflammation and immune dysregulation, leading to ED. ED is marked by reduced nitric oxide (NO) production, increased oxidative stress, and heightened pro-inflammatory and prothrombotic activities, which are crucial in the development of cardiovascular disease (CVD) and systemic inflammation. This association persists even in RD patients without conventional cardiovascular risk factors, suggesting a direct impact of RD-related inflammation on endothelial function. Studies also show that ED significantly contributes to atherosclerosis, thereby elevating cardiovascular risk in RD patients. This review synthesizes the molecular mechanisms connecting major RDs and ED, highlighting potential biomarkers and therapeutic targets. Ultimately, the review aims to enhance understanding of the complex interactions leading to ED in rheumatic patients and inform strategies to mitigate cardiovascular risks and improve patient outcomes.

Keywords: Cardiovascular diseases; Chronic inflammation; Endothelial dysfunction; Immune system dysregulation; Rheumatic diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / pathology
  • Endothelium, Vascular* / physiopathology
  • Humans
  • Inflammation
  • Nitric Oxide / metabolism
  • Oxidative Stress
  • Rheumatic Diseases* / etiology
  • Rheumatic Diseases* / metabolism
  • Rheumatic Diseases* / pathology
  • Rheumatic Diseases* / physiopathology

Substances

  • Biomarkers
  • Nitric Oxide