Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling
Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling
复制标题
原发性高醛固酮血症高血压患者早期内皮祖细胞内皮修复能力受损：5,6,7,8-四氢生物蝶呤氧化和内皮一氧化氮合酶解偶联的作用
DOI：
10.1161/hypertensionaha.115.06597
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发表时间：
2016-02-01
期刊：
影响因子：
8.3
通讯作者：
Tao, Jun
中科院分区：
文献类型：
--
作者：
Chen, Long;Ding, Mei-Lin;Tao, Jun
尽管高醛固酮血症除了升高血压外，还会对血管内皮产生有害影响，但高醛固酮血症对动脉损伤后早期内皮祖细胞（EPC）介导的内皮修复的影响和分子机制尚不清楚。本研究的目的是研究原发性高醛固酮血症（PHA）高血压患者早期内皮细胞的内皮修复能力。通过将早期内皮细胞移植到裸鼠颈动脉内皮剥蚀模型中，评估来自pha （n=20）、年龄和血压匹配的原发性高血压患者（n=20）和年龄匹配的健康受试者（n=20）的体内内皮修复能力。用血流介导的肱动脉扩张法评价人的血管内皮功能。与年龄匹配的健康受试者相比，pha患者和原发性高血压患者体内早期EPCs的内皮修复能力和血流介导的舒张功能均受损；然而，与原发性高血压患者相比，早期EPC体内内皮修复能力和PHAs血流介导的扩张功能受损更为严重。口服螺内酯可改善早期EPC体内内皮修复能力和pha血流介导的扩张。在pha的早期EPCs中发现氧化应激增加，氧化5,6,7,8-四氢生物蝶呤降解，内皮一氧化氮合酶解偶联和一氧化氮生成减少。烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基p47（phox）敲低或补充5,6,7,8-四氢生物蝶呤可减弱内皮一氧化氮合酶解偶联，增强早期内皮细胞的体内内皮修复能力。综上所述，与高血压患者相比，pha患者早期EPCs的内皮修复能力受损更严重，这与矿化皮质激素受体依赖的氧化应激以及随后的5,6,7,8-四氢生物蝶呤降解和内皮一氧化氮合酶解偶联有关。
Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degradation and endothelial nitric oxide synthase uncoupling.