Division of Pharmacology and Toxicology, Center for Drug Evaluation and Research, 10903 New Hampshire Ave., Bldg. 22, Rm. 4178, Silver Spring, MD, USA.
J Cardiovasc Transl Res. 2024 Aug;17(4):851-858. doi: 10.1007/s12265-024-10502-0. Epub 2024 Feb 26.
Following the placement of endovascular implants, perivascular adipose tissue (PVAT) becomes an early sensor of vascular injury to which it responds by undergoing phenotypic changes characterized by reduction in the secretion of adipocyte-derived relaxing factors and a shift to a proinflammatory and pro-contractile state. Thus, activated PVAT loses its anti-inflammatory function, secretes proinflammatory cytokines and chemokines, and generates reactive oxygen species, which are accompanied by differentiation of fibroblasts into myofibroblasts and proliferation of smooth muscle cells. These subsequently migrate into the intima, leading to intimal growth. In addition, periadventitial vasa vasorum undergoes neovascularization and functions as a portal for extravasation of inflammatory infiltrates and mobilization of PVAT resident stem/progenitor cells into the intima. This review focuses on the response of PVAT to endovascular intervention-induced injury and discusses potential therapeutic targets to suppress the PVAT-initiated pathways that mediate the formation of neointima.
血管内植入物放置后,血管周围脂肪组织(PVAT)成为血管损伤的早期传感器,它通过发生表型变化来对此做出反应,其特征是脂肪细胞衍生的舒张因子分泌减少,以及向促炎和促收缩状态转变。因此,激活的 PVAT 失去其抗炎功能,分泌促炎细胞因子和趋化因子,并产生活性氧,同时伴随着成纤维细胞向肌成纤维细胞分化和平滑肌细胞增殖。这些细胞随后迁移到内膜,导致内膜生长。此外,血管外膜周围的小血管发生新生血管形成,并作为炎症浸润物外渗和动员 PVAT 驻留的干细胞/祖细胞进入内膜的门户。本综述重点讨论了 PVAT 对血管内介入诱导损伤的反应,并讨论了抑制介导新生内膜形成的 PVAT 起始途径的潜在治疗靶点。