血管紧张素1-7在人体微循环中的血管作用：端粒酶的新作用。
Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase.
作者信息
Durand Matthew J, Zinkevich Natalya S, Riedel Michael, Gutterman David D, Nasci Victoria L, Salato Valerie K, Hijjawi John B, Reuben Charles F, North Paula E, Beyer Andreas M
机构信息
From the Department of Physical Medicine and Rehabilitation (M.J.D.), Department of Medicine, Cardiovascular Center (M.J.D., N.S.Z., M.R., D.D.G., V.L.N., A.M.B.), Department of Pathology, Division of Pediatric Pathology (V.K.S., P.E.N.), Department of Plastic Surgery (J.B.H.), Department of Cardiothoracic Surgery (C.F.R.), and Department of Physiology (A.M.B.), Medical College of Wisconsin, Milwaukee; and Department of Health and Medicine, Carroll University, Waukesha, WI (N.S.Z.).
出版信息
Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1254-62. doi: 10.1161/ATVBAHA.116.307518. Epub 2016 Apr 14.
OBJECTIVE
This study examined vascular actions of angiotensin 1-7 (ANG 1-7) in human atrial and adipose arterioles.
APPROACH AND RESULTS
The endothelium-derived hyperpolarizing factor of flow-mediated dilation (FMD) switches from antiproliferative nitric oxide (NO) to proatherosclerotic hydrogen peroxide in arterioles from humans with coronary artery disease (CAD). Given the known vasoprotective properties of ANG 1-7, we tested the hypothesis that overnight ANG 1-7 treatment restores the NO component of FMD in arterioles from patients with CAD. Endothelial telomerase activity is essential for preserving the NO component of vasodilation in the human microcirculation; thus, we also tested whether telomerase activity was necessary for ANG 1-7-mediated vasoprotection by treating separate arterioles with ANG 1-7±the telomerase inhibitor 2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid. ANG 1-7 dilated arterioles from patients without CAD, whereas dilation was significantly reduced in arterioles from patients with CAD. In atrial arterioles from patients with CAD incubated with ANG 1-7 overnight, the NO synthase inhibitor NG-nitro-l-arginine methyl ester abolished FMD, whereas the hydrogen peroxide scavenger polyethylene glycol catalase had no effect. Conversely, in vessels incubated with ANG 1-7+2-[[(2E)-3-(2-naphthalenyl)-1-oxo-2-butenyl1-yl]amino]benzoic acid, NG-nitro-l-arginine methyl ester had no effect on FMD, but polyethylene glycol catalase abolished dilation. In cultured human coronary artery endothelial cells, ANG 1-7 significantly increased telomerase activity. These results indicate that ANG 1-7 dilates human microvessels, and dilation is abrogated in the presence of CAD. Furthermore, ANG 1-7 treatment is sufficient to restore the NO component of FMD in arterioles from patients with CAD in a telomerase-dependent manner.
CONCLUSIONS
ANG 1-7 exerts vasoprotection in the human microvasculature via modulation of telomerase activity.
目的
本研究检测了血管紧张素1-7（ANG 1-7）对人房性和脂肪组织小动脉的血管作用。
方法与结果
在冠状动脉疾病（CAD）患者的小动脉中，血流介导的舒张（FMD）的内皮源性超极化因子从抗增殖的一氧化氮（NO）转变为促动脉粥样硬化的过氧化氢。鉴于ANG 1-7已知的血管保护特性，我们检验了以下假设：过夜给予ANG 1-7治疗可恢复CAD患者小动脉中FMD的NO成分。内皮端粒酶活性对于维持人体微循环中血管舒张的NO成分至关重要；因此，我们还通过用ANG 1-7±端粒酶抑制剂2-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸处理不同的小动脉，来检测端粒酶活性对于ANG 1-7介导的血管保护是否必要。ANG 1-7可使无CAD患者的小动脉扩张，而CAD患者小动脉的扩张则显著减弱。在CAD患者的房性小动脉中，过夜孵育ANG 1-7后，一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯消除了FMD，而过氧化氢清除剂聚乙二醇过氧化氢酶则无作用。相反，在用ANG 1-7 + 2-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸孵育的血管中，NG-硝基-L-精氨酸甲酯对FMD无作用，但聚乙二醇过氧化氢酶消除了血管舒张。在培养的人冠状动脉内皮细胞中，ANG 1-7显著增加了端粒酶活性。这些结果表明，ANG 1-7可扩张人体微血管，而在CAD存在时扩张作用被消除。此外，ANG 1-7治疗足以以端粒酶依赖性方式恢复CAD患者小动脉中FMD的NO成分。
结论
ANG 1-7通过调节端粒酶活性在人体微血管中发挥血管保护作用。
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