Implications of Angiogenesis Involvement in Arthritis.
Implications of Angiogenesis Involvement in Arthritis.
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DOI：
10.3390/ijms19072012
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发表时间：
2018-07-10
影响因子：
5.6
通讯作者：
Tang CH
中科院分区：
文献类型：
--
作者：
MacDonald IJ;Liu SC;Su CM;Wang YH;Tsai CH;Tang CH
血管生成，即新血管的生长，在关节炎性疾病（如类风湿关节炎（RA）和骨关节炎（OA））的发病机制中是必不可少的，它促进了炎症细胞的侵袭和局部疼痛受体的增加，从而导致结构损伤和疼痛。血管生成过程是由多种介质持续进行的，如生长因子，主要是血管内皮生长因子（VEGF）和缺氧诱导因子（hif），以及促炎细胞因子、各种趋化因子、基质成分、细胞粘附分子、蛋白酶等。尽管开发了有效的、耐受性良好的非生物（传统）和生物疾病调节剂，极大地改善了RA患者的预后，但许多人仍然对这些疗法有耐药性，只是部分反应，或者不能耐受生物制剂。唯一被批准的OA治疗包括症状缓解剂，如镇痛药、非甾体抗炎药（NSAIDs）、类固醇和透明质酸。没有一种可用的治疗方法可以减缓疾病的进展，恢复原始结构或使受损关节恢复功能。此外，围绕RA和OA的现有治疗方法存在许多安全性问题。需要新的治疗方法，不仅针对炎症关节，控制RA和OA的关节炎症，而且选择性地抑制滑膜血管生成，同时防止健康组织损伤。本文对PubMed上的文献进行了叙述性回顾，重点阐述了在实验性RA和OA中调节血管生成活性的治疗益处。这一证据指出了这些疾病的新治疗靶点。
Angiogenesis, the growth of new blood vessels, is essential in the pathogenesis of joint inflammatory disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA), facilitating the invasion of inflammatory cells and increase in local pain receptors that contribute to structural damage and pain. The angiogenic process is perpetuated by various mediators such as growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as proinflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases, and others. Despite the development of potent, well-tolerated nonbiologic (conventional) and biologic disease-modifying agents that have greatly improved outcomes for patients with RA, many remain resistant to these therapies, are only partial responders, or cannot tolerate biologics. The only approved therapies for OA include symptom-modifying agents, such as analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, and hyaluronic acid. None of the available treatments slow the disease progression, restore the original structure or enable a return to function of the damaged joint. Moreover, a number of safety concerns surround current therapies for RA and OA. New treatments are needed that not only target inflamed joints and control articular inflammation in RA and OA, but also selectively inhibit synovial angiogenesis, while preventing healthy tissue damage. This narrative review of the literature in PubMed focuses on the evidence illustrating the therapeutic benefits of modulating angiogenic activity in experimental RA and OA. This evidence points to new treatment targets in these diseases.