Fibroblast Activation Protein Mediates Vascular Restenosis After Surgery for Peripheral Arterial Disease

Postoperative vascular restenosis is a major obstacle to the long-term efficacy of surgery for peripheral arterial disease (PAD). Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) trigger neointimal hyperplasia, the core pathology of restenosis, while relevant molecular regulators remain poorly defined. This study investigated the expression, function and mechanism of fibroblast activation protein (FAP). Bioinformatics analysis of GEO datasets identified FAP as a candidate factor. FAP showed low expression in normal arteries but was obviously elevated in injured vessels and synthetic VSMCs, and its expression correlated positively with VSMC migration. FAP knockdown restrained VSMC migration in vitro and mitigated neointimal hyperplasia in vivo. RNA sequencing suggested FAP may be involved in regulating the Net1–RhoA–ROCK signaling axis. Collectively, FAP is upregulated in injured arterial tissues and promotes VSMC migration to facilitate neointimal hyperplasia and restenosis, indicating its potential as a biomarker and therapeutic target for PAD-associated restenosis.