Intimal hyperplasia and adventitial angiogenesis originating from veins are vascular remodelling responses in large vessels after major lower extremity trauma induced ischemia

Background: Total paucity exists on how large human blood vessels respond to ischemia. We explored the human vascular response to trauma-induced ischemia, with a particular focus on vascular wall remodelling. Methods: Arterial and venous wall samples were analysed from 40 patients undergoing soft tissue free flap reconstruction following lower extremity trauma. Patients were stratified into an early reconstruction group (median 6 days post-injury (IQR 4–8); n = 26) after high-energy lower extremity open fracture, and a late reconstruction group (median 54 days post-injury (IQR 31–155); n = 14) operated due to fracture non-union or fracture related infection. Injury-site arterial and venous biopsy samples were collected at the anastomosis site during reconstruction, while control samples were obtained from intact blood vessels at free flap donor sites. Quantitative histological and immunohistochemical analyses were performed using QuPath software. Results: The cohort consisted predominantly of working-age males (median age: early group 44 years, late 50 years; p = 0.72). Arterial intimal hyperplasia was significantly greater at injury sites than in the control arteries in both groups. Venous intimal thickening exceeded control levels by more than threefold. Adventitial angiogenesis was primarily observed in veins in the early reconstruction group, and it was more pronounced in both arteries and veins of the late group compared to the early group. Conclusions: Our findings demonstrate that major lower extremity trauma and trauma-induced ischemia trigger active remodelling across all layers of the vascular wall. The most prominent structural changes are linked to rapid onset of intimal hyperplasia and adventitial angiogenesis originating from the venous system.