Background: Long-term saphenous vein graft patency is significantly lower compared to arterial grafts mostly due to accelerated atherosclerosis. Reactive oxygen species were implicated in the pathogenesis of diabetes and hyperlipidemic-induced vascular complications, including accelerated coronary artery bypass graft atherosclerosis. We aimed to characterize the Thioredoxin anti-oxidant system in arterial and venous conduits and correlate its expression with the patients` metabolic state.
Methods: Thioredoxin and Thioredoxin-interacting protein (TXNIP) expression were measured by immunoblot assay in saphenous vein (SV), internal mammary artery (IMA) and radial artery (RA) segments obtained from patients (n=50) undergoing isolated coronary artery bypass grafting. We then correlated Thioredoxin expression with risk factors of atherosclerosis.
Results: The expression of Thioredoxin in the IMA and RA was similar and significantly higher compared to SV (Panel A, p<0.001). TXNIP (inhibitor of Thioredoxin ) levels were undetectable in the SV. Impaired glucose control in diabetic patients with glycosylated hemoglobin levels greater than 6% was associated with a five-fold decrease in Thioredoxin expression in the IMA, but did not have a measurable effect in SV (Panel B, p<0.001), and did not have a measurable effect on TXNIP levels in the IMA . Similarly, serum LDL levels greater than 2.59mM/L were associated with threefold decrease in Thioredoxin expression in the IMA but not in SV (panel C, p<0.001). Serum LDL levels greater than 2.59mM/L were associated with 40% increase in TXNIP levels (p<0.05). Immunohistochimical staining demonstrated expression of Thioredoxin in the endothelial cells layer of the conduit and in the vasa-vasorum.
Conclusion: Arterial conduits express significantly higher amounts of Thioredoxin compared to saphenous veins, rendering them more resilient to oxidative stress and possibly accelerated graft atherosclerosis. This protective mechanism is markedly impaired in patients with poorly controlled diabetes or abnormal lipid profile.
The Thioredoxin system may be a novel therapeutic target to enhance long-term graft patency.
