Abstract 10391: Acute Inflammation Rapidly Increases Plasma Biopterins and Impairs Endothelial Function: A Novel Role of Plasma Tetrahydrobiopterin as a Marker of Acute Inflammation
Background: Tetrahydrobiopterin (BH4) is a co-factor of endothelial nitric oxide synthase (eNOS), essential for the maintenance of its enzymatic coupling. Although vascular BH4 is positively associated with NO bioavailability, the value of circulating BH4 as a biomarker is unknown, since GTPCH, the rate limiting enzyme for its biosynthesis, is up-regulated by inflammation. We examined relationships between circulating BH4 and endothelial function after induction of acute inflammation.
Methods: Twenty healthy young adults were randomized to receive either Salmonella Typhi vaccine or normal saline (placebo) i.m., in a double-blind placebo controlled study. Endothelial function was evaluated in the brachial artery (by flow mediated dilation-FMD) at baseline and 8h, 12h and 24h after the intervention. Blood samples were also obtained at all time-points, to determine circulating c-reactive protein (hsCRP) and interleukin 6 (IL-6) by ELISA, and plasma BH4 and total biopterins (tBio, that include BH4 and its products of oxidation) by HPLC.
Results: Vaccination induced a significant elevation of IL-6 at 8h and 12h, then returned to baseline at 24h (A); hsCRP was increased at 24h (B). Importantly, plasma BH4 and tBio (C) were increased at 8h and 12h following the same pattern as IL-6, while FMD was reduced at the same time points (D).
Conclusions: Acute inflammation induced by S. Typhii vaccine, rapidly increased circulating biopterins, following the same pattern as circulating IL-6. However, endothelial function was reduced in parallel to the increase of plasma biopterins. This discordance between circulating BH4 and endothelial function under conditions of acute inflammation, suggests that circulating biopterins should be considered as a marker of inflammation, and are not directly related to endothelial function.
- © 2011 by American Heart Association, Inc.