Myocardial function with reduced expression of the sodium-calcium exchanger.
Myocardial function with reduced expression of the sodium-calcium exchanger.
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DOI：
10.1016/j.cardfail.2010.03.012
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发表时间：
2010-09
影响因子：
6
通讯作者：
Roos, Kenneth P.
中科院分区：
文献类型：
--
作者：
Jordan, Maria C.;Henderson, Scott A.;Han, Tieyan;Fishbein, Michael C.;Philipson, Kenneth D.;Roos, Kenneth P.
心脏钠钙交换器（NCX 1）的完全去除与胚胎死亡有关，而其过度表达与心力衰竭有关。为了确定NCX 1的表达降低是否与正常心脏结构和功能相容，我们研究了NCX 1水平降低的两种敲除小鼠模型：在所有肌细胞中NCX 1表达水平为50%的杂合整体敲除（HG-KO）和仅在10-20%的肌细胞中表达NCX 1的心室特异性KO（V-KO）。在基线、经主动脉缩窄（TAC）后以及急性或慢性β-肾上腺素能刺激后对两组小鼠进行评价。在基线时，HG-KO小鼠具有较小的心脏，V-KO小鼠具有比其野生型（WT）对照更大的心脏（P<0.05）。HG-KO及其对照WT小鼠对TAC和β-肾上腺素能刺激具有正常反应。然而，与HG-KO小鼠和WT对照相比，V-KO组对TAC不耐受，并且对β-肾上腺素能刺激具有显著（P<0.05）钝化的反应。与HG-KO小鼠不同，V-KO小鼠不耐受慢性异丙肾上腺素输注。心电图、体温和活动的遥测分析显示所有组小鼠的昼夜节律正常，但证实V-KO小鼠的QT间期沿着缩短，心律失常增加，R/P振幅比降低。虽然NCX 1在所有肌细胞中可以减少1/2而没有显著的功能改变，但它必须在超过20%的肌细胞中表达，以防止小鼠心脏的严重重塑和心力衰竭。
The complete removal of the cardiac sodium-calcium exchanger (NCX1) is associated with embryonic lethality while its overexpression is linked to heart failure. To determine whether or not a reduced expression of NCX1 is compatible with normal heart structure and function, we studied two knockout mouse models with reduced levels of NCX1: a heterozygous global knockout (HG-KO) with a 50% level of NCX1 expression in all myocytes, and a ventricular specific KO (V-KO) with NCX1 expression in only 10-20% of the myocytes. Both groups of mice were evaluated at baseline, after trans-aortic constriction (TAC), and after acute or chronic beta-adrenergic stimulation. At baseline, the HG-KO mice had smaller hearts and the V-KO mice had larger hearts than their wild-type (WT) controls (P<0.05). The HG-KO and their control WT mice had normal responses to TAC and beta-adrenergic stimulation. However, the V-KO group was intolerant to TAC and had a significantly (P<0.05) blunted response to beta-adrenergic stimulation as compared to the HG-KO mice and WT controls. Unlike the HG-KO mice, the V-KO mice did not tolerate chronic isoproterenol infusion. Telemetric analysis of the ECG, body temperature and activity revealed a normal diurnal rhythm in all groups of mice, but confirmed shorter QT intervals along with increased arrhythmias and reduced R/P amplitude ratios in the V-KO mice. Though NCX1 can be reduced by ½ in all myocytes without significant functional alterations, it must be expressed in more than 20% of the myocytes to prevent severe remodeling and heart failure in mouse heart.
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影响因子：
20.1
作者：
STUDER, R;REINECKE, H;DREXLER, H
通讯作者：
DREXLER, H
影响因子：
3.5
作者：
Wehling-Henricks, M;Jordan, MC;Tidball, JG
通讯作者：
Tidball, JG
影响因子：
6
作者：
Roos, Kenneth P.;Jordan, Maria C.;Philipson, Kenneth D.
通讯作者：
Philipson, Kenneth D.
影响因子：
20.1
作者：
Imahashi, K;Pott, C;Murphy, E
通讯作者：
Murphy, E
影响因子：
4.8
作者：
Wakimoto, K;Kobayashi, K;Komuro, I
通讯作者：
Komuro, I