血管炎性疾病中的血管粘附蛋白-1 (VAP-1)。,Vasa

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血管炎性疾病中的血管粘附蛋白-1 (VAP-1)。
Vasa Pub Date : 2022-10-06 , DOI: 10.1024/0301-1526/a001031
Marianna Danielli ₁ , Roisin Clare Thomas ₁ , Lauren Marie Quinn ₂ , Bee Kang Tan _{1,

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Affiliation

血管粘附蛋白 1 (VAP-1) 也称为氨基氧化酶铜 3 (AOC3)，是一种具有粘附和酶促特性的促炎和多功能分子。VAP-1 是一种伯胺氧化酶，属于氨基脲敏感型胺氧化酶 (SSAO) 家族，可催化伯胺的氧化，从而产生铵、甲醛、甲基乙二醛和过氧化氢。VAP-1主要由内皮细胞、平滑肌细胞、脂肪细胞和周细胞表达。它涉及一系列生物学功能，例如免疫细胞外渗、血管生成和血管化。在过去的十年中，VAP-1 的研究已经加强，因为它作为一种新的临床生物标志物和作为血管炎性疾病（如动脉粥样硬化、中风、糖尿病、神经血管疾病（例如阿尔茨海默病）、肝病（例如非酒精性脂肪性肝炎）和皮肤病（例如牛皮癣）。这是关于 VAP-1 的最新和最全面的评论，重点关注 VAP-1 的转化方面。与最近的综述相比，我们的综述提供了关于 VAP-1 和心力衰竭、中风和虚弱、糖尿病、子宫内膜异位症、骨关节炎、COVID-19、结膜炎相关系统性红斑狼疮、造血干细胞、神经胶质瘤、结直肠癌治疗的新见解。新型 VAP-1 抑制剂 (U-V269)，使用新型 VAP-1 抑制剂 (PXS-4681A) 和 68Ga-DOTA-Siglec-9，Siglec-9 的标记肽 (a VAP-1 配体），它似乎是类风湿性关节炎炎症的安全 PET 示踪剂。最后，我们展示了 VAP-1 在妊娠中作为免疫细胞的看门人的新兴作用，这些细胞对螺旋动脉重塑至关重要，其缺乏可能导致妊娠血管疾病，如先兆子痫。未来的研究应优先考虑 VAP-1 小分子抑制剂和单克隆抗体的临床试验，从而最大限度地发挥 VAP-1 靶向治疗的潜力，并研究 sVAP-1 作为疾病及其预后的临床生物标志物。

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Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases.

Vascular adhesion protein-1 (VAP-1) also known as amino oxidase copper containing 3 (AOC3) is a pro-inflammatory and versatile molecule with adhesive and enzymatic properties. VAP-1 is a primary amine oxidase belonging to the semicarbazide-sensitive amine oxidase (SSAO) family, which catalyzes the oxidation of primary amines leading to the production of ammonium, formaldehyde, methylglyoxal, and hydrogen peroxide. VAP-1 is mainly expressed by endothelial cells, smooth muscle cells, adipocytes and pericytes. It is involved in a repertoire of biological functions, e.g., immune cell extravasation, angiogenesis, and vascularization. Research into VAP-1 has intensified within the last decade on its role as a novel clinical biomarker and as a potential therapeutic target of vascular inflammatory disorders such as atherosclerosis, stroke, diabetes, neurovascular disorders (e.g., Alzheimer's Disease), hepatic disease (e.g., non-alcoholic steatohepatitis), and skin conditions (e.g., psoriasis). This is the most up-to-date and comprehensive review on VAP-1 focusing on the translational aspects of VAP-1. Compared to recent reviews, our review provides novel insights on VAP-1 and heart failure, stroke and frailty, diabetes, endometriosis, osteoarthritis, COVID-19, conjunctivitis associated systemic lupus erythematosus, hematopoietic stem cells, gliomas, treatment of colorectal cancer with a novel VAP-1 inhibitor (U-V269), promoting recovery of motor functions and habit learning with a novel VAP-1 inhibitor (PXS-4681A), and 68Ga-DOTA-Siglec-9, a labelled peptide of Siglec-9 (a VAP-1 ligand), which appears to be a safe PET tracer for inflammation in rheumatoid arthritis. Finally, we present the emerging role of VAP-1 in pregnancy as a gatekeeper of immune cells, which are critical for spiral arterial remodeling, the deficiency of which could lead to vascular disorders of pregnancy such as preeclampsia. Future research should prioritize clinical trials on VAP-1 small-molecule inhibitors and monoclonal antibodies, thus, maximizing the potential of VAP-1 targeted therapy as well as research into sVAP-1 as a clinical biomarker of diseases and its prognosis.

更新日期：2022-10-06

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