Lentivirus-mediated RNA interference of chymase increases the plaque stability in atherosclerosis in vivo

被引：9

作者：

Guo, Tao ^{[1
,2
]}

Wang, Jie ^{[3
]}

Yang, Jianmin ^{[1
,2
]}

Chen, Wenqiang ^{[1
,2
]}

An, Guipeng ^{[1
,2
]}

Fan, Lu ^{[4
]}

Peng, Qisheng ^{[2
,5
]}

机构：

[1] Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Qilu Hosp, Chinese Minist Hlth, Jinan 250012, Shandong, Peoples R China

[3] Shandong Univ, Qilu Hosp, Dept Phys Med & Rehabil, Jinan 250012, Shandong, Peoples R China

[4] Infect Dis Hosp, Yantai 264000, Shandong, Peoples R China

[5] Jilin Univ, Inst Zoonosis, Key Lab Zoonosis Res, Minist Educ, Changchun 130062, Peoples R China

来源：

EXPERIMENTAL AND MOLECULAR PATHOLOGY | 2013年 / 95卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Atherosclerosis; RNA interference; Chymase; Matrix metalloproteinase 9; PROTEIN-KINASE ALPHA-2; MAST-CELL CHYMASE; MATRIX METALLOPROTEINASES; ACTIVATION; MICE; INHIBITION; MECHANISMS;

D O I：

10.1016/j.yexmp.2013.05.005

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Chymase activity was proved to be closely related with plague vulnerability in a hamster model of atherosclerosis with chymase inhibitors. Considering that chymase inhibitors are nonspecific, here we further investigated the role of chymase in atherosclerosis in vivo through injection of lentivirus containing chymase shRNA or chymase cDNA. Our results revealed that silencing of the chymase gene by shRNA remarkably enhanced atherosclerosis plague stability without alterations in body weight or serum lipid levels. Lentiviral expression of a gain-of-function chymase gene promoted the formation of vulnerable plague in hamsters. Mechanistically, chymase functions as an activator of MMP9 in atherosclerotic lesions that induces plague instability. (c) 2013 Elsevier Inc. All rights reserved.

引用

页码：51 / 56

页数：6

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