Yan Lang, Zhang Ji-Qian-Zhu, Dai Xiao-Yu, Li Jin-Feng, Gao Fang-Yuan, Zhang Xiao-Fang, Tian Yi-Jun, Shi Wen-Jing, Zhu Jiang-Bo, Chen Ji-Kuai
Department of Health Toxicology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China.
Department of Health Toxicology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China,
J Vasc Res. 2021 Feb 8:1-5. doi: 10.1159/000513464.
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.
内皮特异性鸟苷三磷酸环化水解酶I（GTPCH I）过表达（转基因GCH，Tg-GCH）可在体内恢复与衰老相关的内皮功能障碍。检测了年轻和老年小鼠主动脉中GTPCH I的表达以及血清一氧化氮（NO）的释放。将年轻和老年野生型（WT）小鼠以及老年Tg-GCH小鼠的主动脉环悬挂起来进行等长张力记录。采用后肢缺血模型来测量血流恢复情况。老年小鼠主动脉中GTPCH I的表达降低，血清中NO水平下降。与老年WT小鼠相比，Tg-GCH显著提高了老年Tg-GCH小鼠血清中的NO水平，恢复了对乙酰胆碱反应受损的主动脉舒张功能，并显著提高了对L- NAME反应的主动脉收缩功能。重要的是，与老年WT小鼠相比，老年Tg-GCH小鼠的血流恢复显著增加。GTPCH I减少导致与衰老相关的内皮功能障碍，而Tg-GCH可延缓这种功能障碍。
