Open AccessEndothelium-Specific GTP Cyclohydrolase I Overexpression Restores Endothelial Function in Aged Mice
Author(s) -
Yan Ling,
Jiqianzhu Zhang,
Xiaoyu Dai,
Jinfeng Liu,
Fangyuan Gao,
Xiaofang Zhang,
Yijun Tian,
Wenjing Shi,
Jian Zhu,
Ji-Kuai Chen
Publication year - 2021
Publication title -
journal of vascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.58
H-Index - 74
eISSN - 1423-0135
pISSN - 1018-1172
DOI - 10.1159/000513464
Subject(s) - endocrinology , medicine , gtp cyclohydrolase i , endothelium , aorta , endothelial dysfunction , in vivo , acetylcholine , nitric oxide , vasodilation , tetrahydrobiopterin , biology , nitric oxide synthase , microbiology and biotechnology
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.