Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2nd floor, room #281, Belo Horizonte, MG, 30130-100, Brazil.
Department of Pediatrics, Faculty of Medicine, UFMG, Belo Horizonte, Brazil.
Mol Biol Rep. 2021 Sep;48(9):6619-6629. doi: 10.1007/s11033-021-06672-8. Epub 2021 Aug 20.
In rheumatoid arthritis (RA) and osteoarthritis (OA), chronic inflammatory processes lead to progresive joint destruction. The renin-angiotensin system (RAS) is involved in the pathogenesis of RA and OA. The aim of this mini-review article is to summarize evidence on the role of RAS in RA and OA.
A non-systematic search in Pubmed included terms as "rheumatoid arthritis", "renin angiotensin system", "osteopenia", "RANKL", "DKK-1", "MMP", "inflammation", "angiogenesis", "local renin-angiotensin system", "angiotensin converting enzyme", "AT2 receptor", "Ang-(1-7)", "VEGF", "angiotensine receptor blocker", "angiotensin converting enzyme inhibitors", "renin inhibitors".
Both RAS axes, the classical one, formed by angiotensin converting enzyme (ACE), angiotensin (Ang) II and AT1 receptor (AT1R) and the counter-regulatory one, composed by ACE2, Ang-(1-7) and the Mas receptor, modulate inflammation and tissue damage. Ang II activates pro-inflammatory mediators and oxidative stress. Conversely, Ang-(1-7) exerts anti-inflammatory actions, decreasing cytokine release, leukocyte attraction, density of vessels, tissue damage and fibrosis. Angiogenesis facilitates inflammatory cells invasion, while osteopenia causes joint dysfunction. Up-regulated osteoclastogenisis and down-regulated osteoblastogeneses were associaed with the activation of the classical RAS axis. Three different pathways, RANKL, DKK-1 and MMPs are enhanced by classical RAS activation. The treatment of RA included methotrexate and corticosteroids, which can cause side effects. Studies with angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors (ACEi) and renin inhibitors have been conducted in experimental and clinical RA with promising results.
The classical RAS activation is an important mechanism in RA pathogenesis and the benefit of ARB and ACEi administration should be further investigated.
在类风湿关节炎（RA）和骨关节炎（OA）中，慢性炎症过程导致进行性关节破坏。肾素-血管紧张素系统（RAS）参与 RA 和 OA 的发病机制。本文综述的目的是总结 RAS 在 RA 和 OA 中的作用的证据。
在 Pubmed 中进行非系统性检索，包括术语“类风湿关节炎”、“肾素血管紧张素系统”、“骨质疏松症”、“RANKL”、“DKK-1”、“MMP”、“炎症”、“血管生成”、“局部肾素血管紧张素系统”、“血管紧张素转换酶”、“AT2 受体”、“Ang-（1-7）”、“VEGF”、“血管紧张素受体阻滞剂”、“血管紧张素转换酶抑制剂”、“肾素抑制剂”。
经典的 RAS 轴，由血管紧张素转换酶（ACE）、血管紧张素（Ang）II 和 AT1 受体（AT1R）组成，以及拮抗的 RAS 轴，由 ACE2、Ang-（1-7）和 Mas 受体组成，调节炎症和组织损伤。Ang II 激活促炎介质和氧化应激。相反，Ang-（1-7）发挥抗炎作用，减少细胞因子释放、白细胞吸引、血管密度、组织损伤和纤维化。血管生成促进炎症细胞浸润，而骨质疏松症导致关节功能障碍。经典 RAS 轴的激活与破骨细胞生成增加和成骨细胞生成减少有关。三条不同的途径，RANKL、DKK-1 和 MMPs，被经典 RAS 激活增强。RA 的治疗包括甲氨蝶呤和皮质类固醇，这些药物可能会产生副作用。已经在实验性和临床 RA 中进行了使用血管紧张素受体阻滞剂（ARB）、血管紧张素转换酶抑制剂（ACEi）和肾素抑制剂的研究，结果有一定的前景。
经典 RAS 激活是 RA 发病机制中的一个重要机制，ARB 和 ACEi 给药的益处应进一步研究。
