Husaini Arshiya S Anwar, Fathima Aseela, Halawa Dunia, Aakel Nada, Erre Gian Luca, Giordo Roberta, Zayed Hatem, Pintus Gianfranco
Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, 2713, Qatar.
Rheumatology Unit, University Hospital (AOU) of Sassari, Sassari, Italy.
J Mol Med (Berl). 2025 Apr 14. doi: 10.1007/s00109-025-02539-8.
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.
风湿性疾病(RDs)与内皮功能障碍(ED)之间的关系错综复杂且涉及多方面,慢性炎症和免疫系统失调起着关键作用。风湿性疾病包括骨关节炎(OA)、类风湿关节炎(RA)、系统性红斑狼疮(SLE)、强直性脊柱炎(AS)、银屑病关节炎(PsA)、干燥综合征(SS)、系统性硬化症(SSc)、风湿性多肌痛(PMR),其特征为慢性炎症和免疫失调,进而导致内皮功能障碍。内皮功能障碍的特点是一氧化氮(NO)生成减少、氧化应激增加以及促炎和促血栓形成活性增强,这些在心血管疾病(CVD)和全身炎症的发展中至关重要。即使在没有传统心血管危险因素的风湿性疾病患者中,这种关联依然存在,这表明风湿性疾病相关炎症对内皮功能有直接影响。研究还表明,内皮功能障碍显著促进动脉粥样硬化,从而增加风湿性疾病患者的心血管风险。本综述综合了连接主要风湿性疾病和内皮功能障碍的分子机制,突出了潜在的生物标志物和治疗靶点。最终,本综述旨在增进对导致风湿性疾病患者内皮功能障碍的复杂相互作用的理解,并为降低心血管风险和改善患者预后的策略提供依据。