https://scholars.lib.ntu.edu.tw/handle/123456789/515052
標題: | Aldosterone induces tissue inhibitor of metalloproteinases-1 expression and further contributes to collagen accumulation: From clinical to bench studies | 作者: | CHI-SHENG HUNG Chou C.-H. CHE-WEI LIAO Lin Y.-T. Wu X.-M. Chang Y.-Y. YING-HSIEN CHEN VIN-CENT WU MING-JAI SU YI-LWUN HO MING-FONG CHEN YEN-HUNG LIN KWAN-DUN WU |
公開日期: | 2016 | 出版社: | Lippincott Williams and Wilkins | 卷: | 67 | 期: | 6 | 起(迄)頁: | 1309-1320 | 來源出版物: | Hypertension | 摘要: | Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity. ? 2016 American Heart Association, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84968608604&doi=10.1161%2fHYPERTENSIONAHA.115.06768&partnerID=40&md5=df202de1595dc5b3ab2d1ca1b2fc0b36 https://scholars.lib.ntu.edu.tw/handle/123456789/515052 |
ISSN: | 0194-911X | DOI: | 10.1161/HYPERTENSIONAHA.115.06768 | SDG/關鍵字: | aldosterone; collagen; collagen 1a1; eplerenone; glucocorticoid receptor; immunoglobulin enhancer binding protein; interstitial collagenase; messenger RNA; mifepristone; phosphatidylinositol 3 kinase; protein kinase B; small interfering RNA; tissue inhibitor of metalloproteinase 1; unclassified drug; aldosterone; collagen; interstitial collagenase; messenger RNA; TIMP1 protein, human; tissue inhibitor of metalloproteinase 1; adult; aldosterone urine level; animal experiment; Article; bioaccumulation; collagen synthesis; controlled study; diastolic dysfunction; enzyme blood level; enzyme release; female; gene expression; heart fibroblast; heart left ventricle function; heart left ventricle mass; heart muscle fibrosis; human; human cell; in vitro study; in vivo study; major clinical study; male; middle aged; mouse; nonhuman; primary hyperaldosteronism; priority journal; protein expression; transthoracic echocardiography; analysis of variance; animal; C57BL mouse; cardiac muscle; cytology; disease model; fibroblast; fibrosis; gene expression regulation; genetics; hyperaldosteronism; immunohistochemistry; knockout mouse; metabolism; needle biopsy; pathology; pathophysiology; procedures; randomization; real time polymerase chain reaction; signal transduction; Western blotting; Aldosterone; Analysis of Variance; Animals; Biopsy, Needle; Blotting, Western; Collagen; Disease Models, Animal; Female; Fibroblasts; Fibrosis; Gene Expression Regulation; Humans; Hyperaldosteronism; Immunohistochemistry; Male; Matrix Metalloproteinase 1; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Random Allocation; Real-Time Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1 |
顯示於: | 醫學系 |
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