Endothelium-Specific GTP Cyclohydrolase I Overexpression Restores Endothelial Function in Aged Mice

Abstract

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.

Keywords: Aging; Angiogenesis; Endothelial dysfunction; GTP cyclohydrolase I; Nitric oxide.