Overexpression of prostaglandin E2 EP4 receptor improves cardiac function after myocardial infarction.
Overexpression of prostaglandin E2 EP4 receptor improves cardiac function after myocardial infarction.
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DOI：
10.1016/j.yjmcc.2018.03.005
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发表时间：
2018-05
影响因子：
5
通讯作者：
Harding P
中科院分区：
文献类型：
--
作者：
Bryson TD;Gu X;Khalil RM;Khan S;Zhu L;Xu J;Peterson E;Yang XP;Harding P
前列腺素E2 （PGE2）信号通过4种不同的g蛋白偶联受体亚型引发多种生理和病理生理作用。我们最近报道了PGE2通过其EP3受体可以降低离体心肌细胞的心脏收缩力和工作心脏准备。因此，我们假设在衰竭的心脏中存在EP3/EP4比例失衡，并且在心力衰竭的小鼠模型中过度表达EP4会改善心功能。我们的假设在心肌梗死（MI）小鼠模型中得到验证，使用由肌球蛋白重链启动子驱动的AAV9-EP4在心肌细胞中过表达EP4。超声心动图评估心功能。我们发现过表达EP4可改善缩短分数（p=0.0025）、射血分数（p=0.0003）和收缩时左心室尺寸减小（p=0.0013）。EP4过表达还能显著降低心肌肥厚指标和间质胶原含量。用AAV9-EP4处理的动物还能显著降低心肌梗死后tnf - α mRNA的表达、巨噬细胞和T细胞的迁移数量，并降低iNOS的表达。EP4的过表达可改善心肌梗死后的心功能。这可能通过减少不良的心脏重塑或抑制细胞因子/趋化因子的产生来介导。
Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function. Our hypothesis was tested in a mouse model of myocardial infarction (MI) with the use of AAV9-EP4 driven by the myosin heavy chain promoter to overexpress EP4 in the cardiac myocytes. Echocardiography was performed to assess cardiac function. We found that overexpression of EP4 improved shortening fraction (p=0.0025), ejection fraction (p=0.0003), and reduced left ventricular dimension at systole (p=0.0013). Overexpression of EP4 also significantly reduced indices of cardiac hypertrophy and interstitial collagen fraction. Animals treated with AAV9-EP4 also had a significant decrease in TNFα mRNA expression and in the number of macrophages and T cells migrated post MI coupled with a reduction in the expression of iNOS. Overexpression of EP4 improves cardiac function post MI. This may be mediated through reductions in adverse cardiac remodeling or via inhibition of cytokine/chemokine production.
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影响因子：
37.8
作者：
Martin, M;Meyer-Kirchrath, J;Hohlfeld, T
通讯作者：
Hohlfeld, T
影响因子：
20.1
作者：
Spinale, FG;Coker, ML;Hebbar, L
通讯作者：
Hebbar, L
影响因子：
10.8
作者：
Hishikari, Keiichi;Suzuki, Jun-ichi;Isobe, Mitsuaki
通讯作者：
Isobe, Mitsuaki
DOI：
10.1152/ajpheart.00136.2003
发表时间：
2004-04-01
影响因子：
4.8
作者：
LaPointe, MC;Mendez, M;Yang, XP
通讯作者：
Yang, XP
DOI：
10.1152/ajpheart.00207.2003
发表时间：
2003-09-01
影响因子：
4.8
作者：
Hayashidani, S;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A