醛固酮损害血管平滑肌功能：从临床到基础研究
Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research.
作者信息
Chou Chia-Hung, Chen Ying-Hsien, Hung Chi-Sheng, Chang Yi-Yao, Tzeng Yu-Lin, Wu Xue-Ming, Wu Vin-Cent, Tsai Chia-Ti, Wu Cho-Kai, Ho Yi-Lwun, Wu Kwan-Dun, Lin Yen-Hung
机构信息
Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
出版信息
J Clin Endocrinol Metab. 2015 Nov;100(11):4339-47. doi: 10.1210/jc.2015-2752. Epub 2015 Sep 24.
CONTEXT
The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA).
OBJECTIVE
Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation.
DESIGN
We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells.
SETTING
This study took place in an academic clinical research center.
PARTICIPANTS
Participants included 35 patients with PA and 30 patients with EH.
INTERVENTIONS
Adrenalectomy was undertaken in patients with aldosterone-producing adenoma.
RESULTS
The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2.
CONCLUSIONS
Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.
背景
醛固酮对血管平滑肌细胞功能的影响仍不明确。一种测量血管平滑肌细胞功能的方法是内皮依赖性血管舒张，其关键因素是肌浆网钙三磷酸腺苷酶（SERCA）。
目的
我们的目的是研究醛固酮对血管平滑肌细胞功能和SERCA调节的影响。
设计
我们前瞻性分析了35例原发性醛固酮增多症（PA；32例醛固酮瘤患者和3例特发性醛固酮增多症患者）和30例原发性高血压（EH）患者作为对照组。对两组患者以及醛固酮瘤患者肾上腺切除术后1年进行血流介导的舒张和硝酸酯介导的舒张检测。此外，我们研究了醛固酮对人主动脉平滑肌细胞中SERCA调节的影响。
地点
本研究在一个学术临床研究中心进行。
参与者
参与者包括35例PA患者和30例EH患者。
干预措施
对醛固酮瘤患者进行肾上腺切除术。
结果
PA患者的血流介导的舒张（FMD）和硝酸酯介导的舒张（NMD）值显著低于EH患者（FMD：13±6对16±4；NMD：16±6对19±5；P均<.05）。FMD/NMD与24小时尿醛固酮对数显著相关（FMD：r = -0.287, P = .048；NMD：r = -0.402, P = .005），但与血压无关。肾上腺切除术后1年，受损的FMD和NMD值显著恢复（FMD：11±4至19±7；NMD：15±6至21±6；P均<.01）。在共聚焦显微镜下，醛固酮可抑制人主动脉平滑肌细胞中SERCA2a的表达。醛固酮在mRNA和蛋白质水平上从10(-8) M起显著抑制SERCA2a的表达。这种抑制是通过下调盐皮质激素受体依赖性线粒体转录因子A和B2实现的。
结论
醛固酮损害血管平滑肌细胞功能并抑制SERCA 2a表达。
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