Regression of pressure overload-induced left ventricular hypertrophy in mice
Regression of pressure overload-induced left ventricular hypertrophy in mice
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DOI：
10.1152/ajpheart.00836.2004
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发表时间：
2005-06-01
影响因子：
4.8
通讯作者：
Du, XJ
中科院分区：
文献类型：
--
作者：
Gao, XM;Kiriazis, H;Du, XJ
为了探讨压力过载诱导的左心室肥厚（LVH）消退的机制，我们研究了LVH的发展和消退的时间过程，以及伴随的心功能、组织学和基因表达的变化。小鼠分别接受4周或8周的主动脉束带术以建立LVH， 6周解除主动脉束带后LVH开始消退。主动脉束带后左室体积进行性增加，室室逐渐扩张和功能障碍。LVH还与肌细胞增大、间质纤维化以及心房利钠肽、胶原I、胶原III和基质金属蛋白酶-2的表达增强有关，但抑制α -肌球蛋白重链和肌浆网Ca2+- atp酶的表达。主动脉瓣脱带完全或部分逆转LVH、心室扩张和功能障碍、心肌细胞大小、间质纤维化和基因表达模式，每一个都有不同的时间过程。LVH消退的程度取决于压力过载的持续时间，事实证明，在主动脉封带4周的动物中，LVH结构和功能的恢复是完全的，而在主动脉封带8周的动物中，LVH的恢复是不完全的。综上所述，LVH回归包括多种形态、功能和遗传成分，具有不同的时间过程。压力过载时间越长，LVH的恢复速度越慢。
As a prelude to investigating the mechanism of regression of pressure overload-induced left ventricular (LV) hypertrophy (LVH), we studied the time course for the development and subsequent regression of LVH as well as accompanying alterations in cardiac function, histology, and gene expression. Mice were subjected to aortic banding for 4 or 8 wk to establish LVH, and regression was initiated by release of aortic banding for 6 wk. Progressive increase in LV mass and gradual chamber dilatation and dysfunction occurred after aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, and enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metalloproteinase-2 but suppressed expression of alpha-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation and dysfunction, myocyte size, interstitial fibrosis, and gene expression pattern, each with a distinct time course. The extent of LVH regression was dependent on the duration of pressure overload, evidenced by the fact that restoration of LV structure and function was complete in animals subjected to 4 wk of aortic banding but incomplete in animals subjected to 8 wk of aortic banding. In conclusion, LVH regression comprises a variety of morphological, functional, and genetic components that show distinct time courses. A longer period of pressure overload is associated with a slower rate of LVH regression.