Abstract 5221: Plasma Levels of Tetrahydrobiopterin and Endothelial Function Were Improved by Fenofibrate Treatment in Patients With Hypertriglyceridemia
Background: Endothelial nitric oxide synthase (eNOS) catalytic activity becomes “uncoupled” when tetrahydrobiopterin (BH4) is limiting or absent which causes the endothelial function to be impaird. The objective of our study was to investigate the effects of peroxisome proliferator-activated receptor α (PPARα) agonists fenofibrate on plasma levels of nitric oxide (NO) and BH4 and endothelial function in patients with hypertriglyceridemia.
Methods and results: Sixty patients with hypertriglyceridemia were randomly divided into treatment group and the control group. The treatment group (mean follow-up was 145±51 days) was treated with lifestyle changes and fenofibrate 200mg/d; the control group was treated with lifestyle changes only. At the end of the follow-up, plasma NO (99.09±35.51μmol/L vs.121.98±53.27 μmol/L, P < 0.05) and BH4 (1.48±0.79pmol/mL vs. 2.16±1.50pmol/mL, P < 0.05) levels were elevated and plasma homocysteine (Hcy) levels were elevated by 50.1% (P < 0.001) compared with the baseline, coronary flow reserve which reflected coronary endothelial function were improved (2.89±0.78 vs. 3.14±0.67, P < 0.05). Fenofibrate could elevate the plasma BH4 levels (1.39±0.77 pmol/mL vs. 2.31±1.70 pmol/mL, P < 0.01) in patients whose baseline Hcy ≤ 15 μmol/L; but could not change the plasma BH4 levels (1.71±0.83 pmol/mL vs. 1.73±0.58 pmol/mL, P > 0.05) in patients whose baseline Hcy > 15 μmol/L. Furthermore, fenofibrate could elevate plasma BH4 levels only in patients whose Hcy levels ≤15 μmol/L at baseline and at the end of follow-up (1.27±0.78 pmol/mL vs. 2.47±2.07 pmol/mL, P < 0.05), and couldn’t change plasma BH4 levels in patients whose Hcy levels > 15 μmol/L at baseline and at the end of follow-up(1.68±0.87 pmol/mL vs. 1.76±0.61 pmol/mL,P > 0.05).
Conclusion: Fenofibrate can improve endothelial function in patients with hypertriglyceridemia which might relate to the increased expression of NO and BH4 by fenofibrate. Fenofibrate might inhibit the effects of Hcy in decreasing BH4 and impairing of the endothelial function, and elevated Hcy might partially inhibit the effects of fenofibrate in increasing BH4 and improving the vascular endothelial function.