We investigated whether oral tetrahydrobiopterin (BH4) treatment might slow the progression of atherosclerosis using hypercholesterolemic ApoE-knockout (KO) mice. We report that ingesting BH4 in drinking water is effective to inhibit atherogenesis in mice. Furthermore, we report that BH4 treatment improves endothelial dysfunction and attenuates increased mRNA expression of NADPH oxidase components, as well as a number of inflammatory factors, such as LOX-1 and MCP-1, in the aortas of ApoE-KO mice. Strategies such as oral administration of BH4 to ensure continuous BH4 availability may be effective in restoring NO-mediated endothelial function and limiting vascular disease and the progression of atherosclerosis.
