LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion

被引:58
作者
Hu, Changping
Dandapat, Abhijit
Chen, Jiawei
Fujita, Yoshiko
Inoue, Nobutaka
Kawase, Yosuke
Jishage, Kou-ichi
Suzuki, Hiroshi
Sawamura, Tatsuya
Mehta, Jawahar L.
机构
[1] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA
[2] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA
[3] Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410083, Peoples R China
[4] Natl Cardiovasc Ctr, Res Inst, Dept Vasc Physiol, Suita, Osaka 565, Japan
[5] Med Sci Inc, Chugai Res Inst, Gotemba, Shizuoka, Japan
[6] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Res Unit Funct Genom, Obihiro, Hokkaido 080, Japan
[7] Univ Tokyo, Grad Sch Med, Dept Dev & Med Technol, Tokyo, Japan
基金
日本科学技术振兴机构;
关键词
remodeling; ischemia; reperfusion; NADPH oxidase; extracellular matrix;
D O I
10.1016/j.cardiores.2007.07.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Chronic ischemia is associated with alterations in genes that result in myocardial remodeling. An important biochemical basis of cardiac remodeling is generation of reactive oxygen species (ROS). A few studies have suggested that acute ischemia triggers signals for remodeling. We examined the hypothesis that targeted deletion of lectin-like oxidized-LDL receptor (LOX-1) may inhibit signals related to cardiac remodeling. Methods and results: We generated LOX-1 knockout (KO) mice on C57BL/6 (wild-type mice) background, and subjected wild-type and KO mice to ischemia-reperfusion (I-R). The wild-type mice developed a marked reduction in left ventricular systolic pressure and +/- dp/dt(max) and an increase in left ventricular end-diastolic pressure following I-R, and this change was much less in the LOX-1 KO mice, indicating preservation of left ventricular function with LOX-1 deletion. There was evidence for marked oxidative stress (NADPH oxidase expression, malondialdehyde and 8-isoprostane) following I-R in the wild-type mice, much less so in the LOX-1 KO mice (P<0.01). In concert, collagen deposition (Masson's trichrome and Picro-sirius red staining) increased dramatically in the wild-type mice, but only half as much in the LOX-1 KO mice (P<0.01). Collagen staining data was corroborated with procollagen-1 expression. Further, fibronectin and osteopontin expression increased in the wild-type mice, but to a much smaller extent in the LOX-1 KO mice (P<0.01). Conclusions: These findings provide compelling evidence that LOX-1 is a key modulator of cardiac remodeling which starts immediately following I-R. (C) 2007 European Society of Cardiology. Published by Elsevier B.V.
引用
收藏
页码:292 / 302
页数:11
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