Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice
Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice
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DOI：
10.1152/ajpheart.01379.2006
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发表时间：
2007-08-01
影响因子：
4.8
通讯作者：
Huang, Xupei
中科院分区：
文献类型：
--
作者：
Liu, Jing;Du, Jianfeng;Huang, Xupei
心肌肌钙蛋白I(TnI)基因敲除的小鼠在出生后17-18天由于TnI的进行性丢失而表现出猝死的表型。这项研究的目的是深入了解TnI耗竭的生理后果和这些小鼠的死亡原因。用高分辨率超声心动图和多普勒超声心动图对12~17日龄大鼠的心功能进行连续监测。应用高频(类似于20-45 MHz)超声成像系统，对心脏TnI突变纯合子小鼠(cTnI(-/-))和野生型小鼠进行了二维B型和解剖M型超声心动图和多普勒超声心动图检查。在第12天，cTnI(-/-)小鼠在心率、心房和左室(LV)腔大小、LV后壁厚度和体重方面与野生型小鼠没有区别。到了第16天到第17天，由于正常生长，野生型小鼠的心脏内径增加了40%，而cTnI(-/-)小鼠的心房内径增加了97%，而心室内径减少了70%。二尖瓣多普勒分析显示，只有cTnI(-/-)小鼠的等容舒张期延长，二尖瓣E/A比值(早期心室充盈波与晚期心房收缩充盈波)显著倒置，表明左室舒张功能受损。CTnI(-/-)小鼠的心脏在第17天表现出明显的衰竭迹象，特征是心输出量、射血分数和短轴缩短率下降了50%。B型超声心动图显示，此时左室管状变窄，心房增大。在这个模型中，我们的数据与TnI缺乏导致左室舒张功能受损，从而导致舒张性心力衰竭是一致的。
Cardiac troponin I (TnI) knockout mice exhibit a phenotype of sudden death at 17-18 days after birth due to a progressive loss of TnI. The objective of this study was to gain insight into the physiological consequences of TnI depletion and the cause of death in these mice. Cardiac function was monitored serially between 12 and 17 days of age by using high-resolution ultrasonic imaging and Doppler echocardiography. Two-dimensional B-mode and anatomical M-mode imaging and Doppler echocardiography were performed using a high-frequency ( similar to 20-45 MHz) ultrasound imaging system on homozygous cardiac TnI mutant mice ( cTnI(-/-)) and wild-type litter-mates. On day 12, cTnI(-/-) mice were indistinguishable from wildtype mice in terms of heart rate, atrial and LV ( LV) chamber dimensions, LV posterior wall thickness, and body weight. By days 16 through 17, wild-type mice showed up to a 40% increase in chamber dimensions due to normal growth, whereas cTnI(-/-) mice showed increases in atrial dimensions of up to 97% but decreases in ventricular dimensions of up to 70%. Mitral Doppler analysis revealed prolonged isovolumic relaxation time and pronounced inversion of the mitral E/A ratio ( early ventricular filling wave-to-late atrial contraction filling wave) only in cTnI(-/-) mice indicative of impaired LV relaxation. cTnI(-/-) mouse hearts showed clear signs of failure on day 17, characterized by > 50% declines in cardiac output, ejection fraction, and fractional shortening. B-mode echocardiography showed a profoundly narrowed tube-like LV and enlarged atria at this time. Our data are consistent with TnI deficiency causing impaired LV relaxation, which leads to diastolic heart failure in this model.