The human internal thoracic artery releases more nitric oxide in response to vascular endothelial growth factor than the human saphenous vein

Abstract

Objective: Endothelial nitric oxide inhibits smooth muscle cell proliferation, reducing the chance of vascular intimal thickening. In this study we investigated whether the superior long-term patency of the internal thoracic artery in human coronary bypass grafting compared with that of the saphenous vein could be explained by different levels of nitric oxide production.

Methods: The baseline endogenous nitric oxide production appeared to be 50% higher in the internal thoracic artery than in the saphenous vein. Previously, it was shown that vascular endothelial growth factor and the vascular endothelial growth factor receptors KDR (Flk-1) and Flt-1 are expressed in both internal thoracic arteries and saphenous veins and that vascular endothelial growth factor receptor density was higher in internal thoracic arteries than in saphenous veins. Therefore, we also investigated the influence of vascular endothelial growth factor on nitric oxide release in both the internal thoracic artery and the saphenous vein.

Results: Vascular endothelial growth factor augmented nitric oxide production by approximately 50% in the saphenous vein and 100% in the internal thoracic artery. As shown by means of immunohistochemistry, expression of endothelial constitutive nitric oxide synthase was similar in the internal thoracic artery and the saphenous vein, and no inducible nitric oxide synthase was expressed in any of the vascular segments.

Conclusion: Vascular endothelial growth factor augments endothelial constitutive nitric oxide synthase-dependent nitric oxide release to a greater extent in the internal thoracic artery than in the saphenous vein. These findings may help to explain the long-term superiority of the internal thoracic artery versus the saphenous vein as a conduit for coronary artery bypass.