Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction.
Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction.
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DOI：
10.1136/hrt.2008.150128
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Field LJ
中科院分区：
文献类型：
--
作者：
Hassink RJ;Nakajima H;Nakajima HO;Doevendans PA;Field LJ
在心肌细胞中表达主要干扰p193蛋白的转基因小鼠(MHC-1152停止小鼠)表现出诱导细胞周期活动和改变实验性心肌梗死(MI)后的重塑。我们假设，与非转基因小鼠相比，MHC-1152停止心肌梗死后，改变的重塑将导致心功能的改善。MHC-1152Stop小鼠和非转基因仔鼠通过冠状动脉永久闭塞造成实验性心肌梗死。在心肌梗死后24小时和4周测定心肌梗死面积，并在心肌梗死后4周测量左心室压力-容量。四唑盐染色显示，心肌梗死后24小时，MHC-1152停用小鼠和非转基因小鼠的脑梗塞面积无统计学差异。形态计量学分析显示，在MHC-1152停药小鼠中，心肌梗死后4周的梗死区瘢痕扩张减少了10%(p<；0.05)。在假手术的MHC-1152停止小鼠和它们的非转基因小鼠之间，没有发现心功能的差异。然而，在心肌梗死后4周，心肌梗死组小鼠的左心室等容松弛时间常数(Tau)比非转基因小鼠降低了19%(p<；0.05)，dp/dtmax-EDV关系斜率增加了99%(p<；0.05)。在心肌梗死后4周，显性干扰p193基因的表达导致心肌梗死后瘢痕扩张减少，并保留了心肌功能。抑制p193活性可能是治疗心肌梗死的一个重要策略。
Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodeling following experimental myocardial infarction (MI). We hypothesized that the altered remodeling would result in improved cardiac function in the MHC-1152stop mice following MI, as compared to non-transgenic mice. MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 hrs and at 4 weeks post-MI, and left ventricular pressure-volume measurements were performed at 4 weeks post-MI in infarcted and sham-operated animals. Infarct size in MHC-1152stop mice and non-transgenic littermates was not statistically different at 24 hrs post-MI, as measured by tetrazolium staining. Morphometric analysis revealed that infarct scar expansion at 4 weeks post-MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks post-MI ventricular isovolumic relaxation time constant (Tau) was decreased by 19% (p<0.05), and the slope of the dP/dtmax-EDV relationship was 99% increased (p<0.05), in infarcted MHC-1152stop mice as compared to infarcted non-transgenic littermates. Expression of the dominant interfering p193 transgene resulted in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks post-MI. Antagonization of p193 activity may represent an important strategy for the treatment of MI.
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影响因子：
20.1
作者：
Ito, K;Yan, X;Lorell, BH
通讯作者：
Lorell, BH
影响因子：
--
作者：
KATZ, EB;STEINHELPER, ME;FIELD, LJ
通讯作者：
FIELD, LJ
影响因子：
20.1
作者：
Litwin, SE;Zhang, DF;Bridge, JHB
通讯作者：
Bridge, JHB
DOI：
10.1073/pnas.1733908100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Arai, T;Kasper, JS;DeCaprio, JA
通讯作者：
DeCaprio, JA
影响因子：
10.5
作者：
Engel, FB;Schebesta, M;Keating, MT
通讯作者：
Keating, MT