Abstract 469: Altered Plasma vs. Vascular Biopterins In Human Atherosclerosis Reveal Relationships Between Endothelial Nitric Oxide Synthase Coupling, Endothelial Function And Inflammation
Introduction: Tetrahydrobiopterin (BH4) is a regulator of endothelial nitric oxide synthase (eNOS) coupling but its synthesis is also stimulated by inflammation in experimental models. We defined for the first time, the relationships between plasma and vascular biopterins in patients with coronary artery disease, and we determined the impact of BH4 on endothelial function, eNOS coupling, and O2- production in human vessels.
Methods: Paired samples of saphenous veins (SV) and internal mammary arteries (IMA) were obtained from 219 patients undergoing coronary bypass surgery. Vasomotor responses to acetylcholine (Ach) were determined ex-vivo and vascular O2- (± the eNOS inhibitor LNAME) was measured by chemiluminescence. Biopterins were measured by HPLC.
Results: High vascular BH4 was associated with better vasorelaxations of SV to Ach, whereas high plasma BH4 was associated with worse vasorelaxations (Fig. a-b⇓). There was an inverse association between plasma and vascular biopterins (Fig c⇓). High vascular (but not plasma) BH4 was associated with lower O2-and less L-NAME inhibitable O2- (suggesting better eNOS coupling) in both SV and IMA (Fig c⇓). Finally, serum C-reactive protein was correlated with plasma biopterins (r=0.268, p=0.001) but not with vascular biopterins in SV (r=0.02, p=0.0857) or IMA (r=−0.044, p=0.717).
Conclusions: There is an inverse association between plasma and vascular biopterins in patients with atherosclerosis. Vascular but not plasma BH4 is a modulator of NO bioavailability and eNOS coupling in human vessels, while plasma total biopterin is rather a marker of systemic inflammation, than a regulator of vascular function in vivo.