Petzinna Simon M, Bauer Claus-Jürgen, Schäfer Valentin S
Department of Rheumatology and Clinical Immunology, Clinic of Internal Medicine III, University Hospital of Bonn, Bonn, Germany.
Front Med (Lausanne). 2024 Aug 14;11:1448157. doi: 10.3389/fmed.2024.1448157. eCollection 2024.
Vascular adhesion protein-1 (VAP-1) is a type 2 transmembrane sialoglycoprotein with oxidative deamination functionality, encoded by the amine oxidase copper-containing 3 (AOC3) gene. VAP-1 is widely expressed across various tissues, particularly in highly vascularized tissues and organs essential for lymphocyte circulation. In the vascular system, VAP-1 is predominantly found in vascular smooth muscle cells and endothelial cells, with higher expression levels in vascular smooth muscle cells. Under inflammatory conditions, VAP-1 rapidly translocates to the endothelial cell surface, facilitating leukocyte adhesion and migration through interactions with specific ligands, such as sialic acid-binding immunoglobulin-type lectins (Siglec)-9 on neutrophils and monocytes, and Siglec-10 on B cells, monocytes, and eosinophils. This interaction is crucial for leukocyte transmigration into inflamed tissues. Furthermore, VAP-1's enzymatic activity generates hydrogen peroxide and advanced glycation end-products, contributing to cytotoxic damage and vascular inflammation. In this context, the soluble form of VAP-1 (sVAP-1), produced by matrix metalloproteinase cleavage from its membrane-bound counterpart, also significantly influences leukocyte migration. This review aims to elucidate the multifaceted pathophysiological roles of VAP-1 in vascular inflammation, particularly in giant cell arteritis (GCA) and associated polymyalgia rheumatica (PMR). By exploring its involvement in immune cell adhesion, migration, and its enzymatic contributions to oxidative stress and tissue damage, we investigate the importance of VAP-1 in GCA. Additionally, we discuss recent advancements in imaging techniques targeting VAP-1, such as [Ga]Ga-DOTA-Siglec-9 PET/CT, which have provided new insights into VAP-1's role in GCA and PMR. Overall, understanding VAP-1's comprehensive roles could pave the way for improved strategies in managing these conditions.
血管黏附蛋白-1（VAP-1）是一种具有氧化脱氨功能的2型跨膜唾液酸糖蛋白，由含铜胺氧化酶3（AOC3）基因编码。VAP-1在各种组织中广泛表达，尤其在淋巴细胞循环所必需的高度血管化组织和器官中。在血管系统中，VAP-1主要存在于血管平滑肌细胞和内皮细胞中，在血管平滑肌细胞中的表达水平更高。在炎症条件下，VAP-1迅速转移到内皮细胞表面，通过与特定配体相互作用促进白细胞黏附和迁移，这些配体如中性粒细胞和单核细胞上的唾液酸结合免疫球蛋白样凝集素（Siglec）-9，以及B细胞、单核细胞和嗜酸性粒细胞上的Siglec-10。这种相互作用对于白细胞迁移到炎症组织至关重要。此外，VAP-1的酶活性产生过氧化氢和晚期糖基化终产物，导致细胞毒性损伤和血管炎症。在这种情况下，由基质金属蛋白酶从其膜结合对应物上切割产生的可溶性VAP-1（sVAP-1）也显著影响白细胞迁移。本综述旨在阐明VAP-1在血管炎症中的多方面病理生理作用，特别是在巨细胞动脉炎（GCA）和相关的风湿性多肌痛（PMR）中。通过探讨其在免疫细胞黏附、迁移中的作用以及其对氧化应激和组织损伤的酶促贡献，我们研究了VAP-1在GCA中的重要性。此外，我们讨论了针对VAP-1的成像技术的最新进展，如[镓]Ga-DOTA-Siglec-9 PET/CT，它为VAP-1在GCA和PMR中的作用提供了新的见解。总体而言，了解VAP-1的全面作用可为管理这些疾病的改进策略铺平道路。
