CHF1/Hey2 promotes physiological hypertrophy in response to pressure overload through selective repression and activation of specific transcriptional pathways.
CHF1/Hey2 promotes physiological hypertrophy in response to pressure overload through selective repression and activation of specific transcriptional pathways.
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CHF1/Hey2 通过选择性抑制和激活特定转录途径，促进生理肥大，以应对压力超负荷。
DOI：
10.1089/omi.2009.0086
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chin,MichaelT
中科院分区：
文献类型：
--
作者：
Yu,Man;Liu,Yonggang;Xiang,Fan;Li,Yuxin;Cullen,Darragh;Liao,Ronglih;Beyer,RichardP;Bammler,TheodorK;Chin,MichaelT
我们以前已经发现CHF 1/Hey 2阻止苯肾上腺素诱导的心脏肥大的发展。为了确定CHF 1/Hey 2在压力超负荷肥大中的作用，我们对心肌中过量表达CHF 1/Hey 2的野生型和转基因小鼠进行升主动脉结扎。我们发现野生型和转基因小鼠在主动脉结扎后1周心室重量与体重的比值增加。与术前超声心动图和假手术对照组相比，野生型小鼠在1周后也出现缩短分数降低。相比之下，转基因小鼠表现出保留的缩短分数。组织学检查显示，野生型心脏广泛的纤维化，但在转基因心脏纤维化最小。TUNEL染色显示野生型心脏的细胞凋亡增加，但在转基因心脏中没有。将野生型和转基因动物培养的新生心肌细胞暴露于过氧化氢（一种有效的细胞凋亡诱导剂）中，表明野生型细胞的细胞凋亡增加。基因集分析的微阵列数据从野生型和转基因心脏1周后显带抑制和激活的多个途径，涉及细胞凋亡，细胞信号，和生物合成。这些发现表明，CHF 1/Hey 2通过抑制细胞凋亡和调节多种转录途径促进生理性肥大超过病理性肥大。这些发现还表明，CHF 1/Hey 2及其下游通路为新型心力衰竭药物的发现提供了多种靶点，CHF 1/Hey 2的遗传多态性可能影响肥大和心力衰竭的易感性。
We have previously found that CHF1/Hey2 prevents the development of phenylephrine-induced cardiac hypertrophy. To determine the role of CHF1/Hey2 in pressure overload hypertrophy, we performed ascending aortic banding on wild-type and transgenic mice overexpressing CHF1/Hey2 in the myocardium. We found that both wild-type and transgenic mice developed increased ventricular weight to body weight ratios 1 week after aortic banding. Wild-type mice also developed decreased fractional shortening after 1 week when compared to preoperative echocardiograms and sham-operated controls. Transgenic mice, in comparison, demonstrated preserved fractional shortening. Histological examination of explanted heart tissue demonstrated extensive fibrosis in wild-type hearts, but minimal fibrosis in transgenic hearts. TUNEL staining demonstrated increased apoptosis in the wild-type hearts but not in the transgenic hearts. Exposure of cultured neonatal myocytes from wild-type and transgenic animals to hydrogen peroxide, a potent inducer of apoptosis, demonstrated increased apoptosis in the wild-type cells. Gene Set Analysis of microarray data from wild-type and transgenic hearts 1 week after banding revealed suppression and activation of multiple pathways involving apoptosis, cell signaling, and biosynthesis. These findings demonstrate that CHF1/Hey2 promotes physiological over pathological hypertrophy through suppression of apoptosis and regulation of multiple transcriptional pathways. These findings also suggest that CHF1/Hey2 and its downstream pathways provide a variety of targets for novel heart failure drug discovery, and that genetic polymorphisms in CHF1/Hey2 may affect susceptibility to hypertrophy and heart failure.
体外冲击波碎石术治疗肾结石：100 例患者的短期观察。
影响因子：
19.7
作者：
Grantham,JR;Millner,MR;Kaude,JV;Finlayson,B;Hunter2nd,PT;Newman,RC
通讯作者：
Newman,RC