Background Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long‐term venous graft patency secondary to intimal hyperplasia ( IH ) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation ( PTP ) treatment of vein grafts modulates smooth muscle cell ( SMC ) proliferation and migration, and inhibits development of IH . Methods and Results PTP was performed at increasing fluences up to 120 J/cm 2 on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm 2 (median, interquartile range [ IQR ]). At 90 J/cm 2 , PTP ‐treated vessels had a 10‐fold greater Young's modulus than untreated controls (954 [ IQR , 2217] vs 99 kPa [ IQR , 63]; P =0.03). Each pig received a PTP ‐treated and untreated carotid artery venous interposition graft. At 4‐weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 ( IQR , 1.2) and 1.3 mm 2 ( IQR , 0.97; P ≤0.001) in untreated and PTP ‐treated grafts, respectively. Medial area was 9.2 ( IQR , 3.2) and 4.7 mm 2 ( IQR , 2.0; P ≤0.001) in untreated and PTP ‐treated grafts, respectively. Immunohistochemistry was performed to assess alpha‐smooth muscle actin ( SMA ) and proliferating cell nuclear antigen ( PCNA ). Objectively, there were less SMA ‐positive cells within the intima/media of PTP ‐treated vessels than controls. There was an increase in PCNA ‐positive cells within control vein grafts (18% [ IQR , 5.3]) versus PTP ‐treated vein grafts (5% [ IQR , 0.9]; P =0.02). Conclusions By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH .
