Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
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DOI：
10.1016/j.yjmcc.2018.11.014
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发表时间：
2019-02-01
影响因子：
5
通讯作者：
Donato, Anthony J.
中科院分区：
文献类型：
--
作者：
Morgan, R. Garrett;Walker, Ashley E.;Donato, Anthony J.
大弹性和阻力动脉中的血管功能障碍与微血管灌注减少和血压升高有关。最近的证据表明，端粒脱帽诱导的血管细胞衰老可能是氧化应激和血管功能障碍的一个重要来源，但这些过程之间的因果关系尚未阐明。为了验证这一重要的未探索的假设，我们测量了动脉衰老信号和氧化应激，颈动脉和肠系膜动脉内皮依赖性血管舒张能力，肠系膜微血管灌注和内皮糖萼恶化的标志物，以及在一种新的小鼠模型中的血压Cre诱导的全身Trf2缺失和端粒脱帽。Trf2缺失导致动脉衰老信号转导增加320%（P
Age-related vascular dysfunction in large elastic and resistance arteries is associated with reductions in micro vascular perfusion and elevations in blood pressure. Recent evidence indicates that telomere uncapping-induced senescence in vascular cells may be an important source of oxidative stress and vascular dysfunction in aging, but the causal relationship between these processes has yet to be elucidated. To test this important unexplored hypothesis, we measured arterial senescence signaling and oxidative stress, carotid and mesenteric artery endothelium-dependent vasodilatory capacity, markers of mesenteric microvascular perfusion and endothelial glycocalyx deterioration, and blood pressure in a novel mouse model of Cre-inducible whole body Trf2 deletion and telomere uncapping. Trf2 deletion led to a 320% increase in arterial senescence signaling (P