Endothelial Function and Vein Graft Remodeling

Despite the acceptance of catheter-based approaches to lower extremity reconstruction, bypass with autogenous vein remains the most durable option. In the United States alone there are approximately 100,000 lower extremity bypass procedures performed yearly. However, 30-50% of these grafts either occlude or require revision in the first 5 years. Traditional Framingham cardiovascular risk factors such as dyslipidemia and diabetes do not predict which grafts are at risk for failure. Therefore other variables such as hemodynamic factors or endothelial function may be important in identifying vulnerable vein grafts. The applicant has previously noted that vein grafts undergo dramatic geometric remodeling within the first month after implantation into the arterial circulation. This is partly driven by hemodynamic forces such as shear stress and is thought to be related to endothelial function. Shear stress is positively correlated with early (0-1 month) luminal enlargement. This adaptive response is important to maintain bypass graft patency. However, there is considerable amount of variability in this response unaccounted for by shear stress alone. The applicant has further shown that baseline systemic inflammation dampens the ability for adequate vein graft luminal expansion and therefore may uncouple the mechano-chemical signal transduction at the endothelial level. Therefore, this study will examine the relationship between circulating levels of inflammatory mediators and endothelial function in a cohort of patients undergoing lower extremity arterial reconstruction with autogenous vein.