Prevention of Mechanical Stretch-Induced Endothelial and Smooth Muscle Cell Injury in Experimental Vein Grafts

Abstract

Vein grafts are subject to increased tensile stress due to exposure to arterial blood pressure, which has been hypothesized to induce endothelial cell (EC) and smooth muscle cell (SMC) injury. This study was designed to verify this hypothesis and to develop a tissue engineering approach that can be used to prevent these pathological events. Two experimental models were created in rats to achieve these goals: (1) a nonengineered vein graft with increased tensile stress, which was created by grafting a jugular vein into the abdominal aorta using a conventional end-to-end anastomotic technique; and (2) an engineered vein graft with reduced tensile stress, which was created by restricting a vein graft into a cylindrical sheath constructed using a polytetrafluoroethylene membrane. The integrity of ECs in these models was examined by using a silver nitrate staining method, and the integrity of SMCs was assessed by using a fluorescein phalloidin-labeling technique. It was found that nonengineered vein grafts were associated with early EC denudation with a change in EC coverage from 100 percent in normal jugular veins to 36±10, 28±12, 18±9, 44±15, 80±13, and 97±6 percent at 1 and 6 hours and 1, 5, 10, and 30 days, respectively. Similarly, rapid SMC actin filament degradation was found during the early period with a change in SMC coverage from ∼94 percent in normal jugular veins to 80±10, 41±17, 25±9, 51±15, 79±15, 98±2 percent at 1 and 6 hours and 1, 5, 10, and 30 days, respectively, in nonengineered vein grafts. In engineered vein grafts with reduced tensile stress, EC denudation and SMC actin filament degradation were prevented significantly. These results suggested that mechanical stretch due to increased tensile stress contributed to EC and SMC injury in experimental vein grafts, and these pathological events could be partially prevented when tensile stress was reduced by using a biomechanical engineering approach. [S0148-0731(00)00701-9]