Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats
文献类型：期刊论文
| 作者 | Jiang, Baohong1 ; Li, Defang1,2; Deng, Yanping1; Teng, Fukang1,3; Chen, Jing1; Xue, Song4; Kong, Xiangqian1; Luo, Cheng1; Shen, Xu1; Jiang, Hualiang1
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| 刊名 | PLOS ONE
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| 出版日期 | 2013-03-22 |
| 卷号 | 8期号:3 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0059621 |
| 文献子类 | Article |
| 英文摘要 | Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9) contributes to the underlying mechanism. Therefore, new therapeutic strategies to attenuate the effects of MMP-9 are urgently needed. In the present study, we characterize salvianolic acid A (SalA) as a novel MMP-9 inhibitor at molecular, cellular and animal level. We expressed a truncated form of MMP-9 which contains only the catalytic domain (MMP-9 CD), and used this active protein for enzymatic kinetic analysis and Biacore detection. Data generated from these assays indicated that SalA functioned as the strongest competitive inhibitor of MMP-9 among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast, SalA inhibited fibroblast migration, blocked myofibroblast transformation, inhibited secretion of intercellular adhesion molecule (ICAM), interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as collagen induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in heart of spontaneously hypertensive rats (SHR) in vivo. Moreover, SalA treatment in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy. These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its analogues for their potential clinical application of cardioprotection are warranted. |
| WOS关键词 | DIASTOLIC DYSFUNCTION ; TISSUE INHIBITOR ; HEART-FAILURE ; FIBROSIS ; FIBROBLAST ; METALLOPROTEINASE-1 ; MYOFIBROBLASTS ; MILTIORRHIZAE ; ACTIVATION ; EXPRESSION |
| 资助项目 | National Natural Science Foundation of China[81173587] ; National Natural Science Foundation of China[91029704] ; State Key Laboratory of Drug Research[SIMM1203KF-04] ; National Science and Technology Major Project for "Key New Drug Creation and Manufacturing Program"[2013ZX09103002-024] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000316549400074 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277691]  |
| 专题 | 上海中药现代化研究中心 |
| 通讯作者 | Jiang, Baohong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 2.China Pharmaceut Univ, Coll Tradit Chinese Med, Nanjing, Jiangsu, Peoples R China; 3.Shenyang Pharmaceut Univ, Shenyang, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Cardiovasc Surg, Shanghai 200030, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Baohong,Li, Defang,Deng, Yanping,et al. Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats[J]. PLOS ONE,2013,8(3). |
| APA | Jiang, Baohong.,Li, Defang.,Deng, Yanping.,Teng, Fukang.,Chen, Jing.,...&Guo, De-an.(2013).Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats.PLOS ONE,8(3). |
| MLA | Jiang, Baohong,et al."Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats".PLOS ONE 8.3(2013). |
入库方式： OAI收割
来源：上海药物研究所
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