Sabi Essa M, Singh Anuja, Althafar Ziyad M, Behl Tapan, Sehgal Aayush, Singh Sukhbir, Sharma Neelam, Bhatia Saurabh, Al-Harrasi Ahmed, Alqahtani Hosam M, Bungau Simona
Department of Pathology, Clinical Biochemistry Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India.
Inflammopharmacology. 2022 Jun;30(3):737-748. doi: 10.1007/s10787-022-00974-4. Epub 2022 Apr 1.
Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a result of this understanding, anti-inflammatory drugs have been created, perhaps widely effective (like steroids) and highly specialized methods (including anti-TNF antibody) using biological therapies (including TNF inhibitors). Despite this, the connections between inflammatory response, articular development, and intracellular responsiveness to changes in oxygen concentration are undervalued in rheumatoid arthritis. Hypoxia, or a lack of oxygen, is thought to cause enhanced synovial angiogenesis in RA, which is mediated by some of the hypoxia-inducible factors like vascular endothelial growth factor (VEGF). Substantial genetic alterations occur when the HIF regulatory factors signaling cycle is activated, allowing organelles, tissues, and species to acclimatize to decreasing oxygen saturation. The most well-characterized hypoxia-responsive transcripts are the angiogenic stimulant VEGF, whose production is greatly elevated by hypoxia in several types of cells, especially RA synovium fibroblasts. Blocking vascular endothelial growth factors has been demonstrated to be helpful in murine models of rheumatism, indicating how hypoxia could trigger the angiogenesis process, resulting in the progression of RA. These mechanisms highlight the intimate affiliation amongst hypoxia, angiogenesis, and inflammation in rheumatoid arthritis. This review will look at how hypoxia activates molecular pathways and how other pathways involving inflammatory signals develop and sustain synovitis in rheumatoid arthritis.
类风湿关节炎（RA）是一种慢性多因素疾病，具有刺激性和退行性，是一种自身免疫性疾病，影响着全球数百万人。基于这种认识，人们研发出了抗炎药物，可能有广泛的疗效（如类固醇），以及使用生物疗法（包括肿瘤坏死因子抑制剂）的高度专业化方法（包括抗TNF抗体）。尽管如此，炎症反应、关节发育以及细胞内对氧浓度变化的反应之间的联系在类风湿关节炎中并未得到充分重视。缺氧，即氧气缺乏，被认为会导致类风湿关节炎中滑膜血管生成增强，这是由一些缺氧诱导因子如血管内皮生长因子（VEGF）介导的。当缺氧诱导因子（HIF）调节因子信号循环被激活时，会发生大量基因改变，使细胞器、组织和物种能够适应不断降低的氧饱和度。最具特征的缺氧反应性转录本是血管生成刺激因子VEGF，其在几种类型的细胞中，尤其是类风湿关节炎滑膜成纤维细胞中，会因缺氧而大量增加。在风湿病的小鼠模型中，阻断血管内皮生长因子已被证明是有帮助的，这表明缺氧如何触发血管生成过程，导致类风湿关节炎的进展。这些机制突出了类风湿关节炎中缺氧、血管生成和炎症之间的密切联系。本综述将探讨缺氧如何激活分子途径，以及其他涉及炎症信号的途径如何在类风湿关节炎中引发和维持滑膜炎。
