Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.
Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.
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INO80的内皮缺失破坏了冠状动脉生成并引起先天性心脏病。
DOI：
10.1038/s41467-017-02796-3
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发表时间：
2018-01-25
影响因子：
16.6
通讯作者：
Red-Horse K
中科院分区：
文献类型：
--
作者：
Rhee S;Chung JI;King DA;D'amato G;Paik DT;Duan A;Chang A;Nagelberg D;Sharma B;Jeong Y;Diehn M;Wu JC;Morrison AJ;Red-Horse K
在发育过程中，成熟的、功能良好的心脏的形成需要在妊娠中期将心室壁从松散的小梁网络转变为致密的致密心肌。在人类中，不能压实与先天性疾病如左心室致密化不全（LVNC）有关。然而，调节心肌致密化的机制仍然知之甚少。在这里，我们表明，在血管内皮细胞中的Ino80染色质重塑的删除，防止在发展中的小鼠心脏心室致密化。这与有缺陷的冠状动脉血管形成和特异性缺失的Ino80在两个主要的冠状动脉祖组织静脉窦和心内膜的原因中间表型。在体外，内皮细胞以Ino80依赖性方式促进心肌扩张，而不依赖于血流。Ino80缺失增加了E2F激活基因的表达和内皮细胞S期占有率。因此，Ino80对于冠状动脉血管生成至关重要，并允许冠状动脉血管支持心脏壁的适当压实。心脏发育需要在妊娠中期将心室壁致密化为致密心肌。在这里，Rhee及其同事表明，染色质重塑Ino80对冠状血管的形成至关重要，并表明在胚胎发育期间，冠状血管是成功的心脏致密化所必需的。
During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues—sinus venosus and endocardium—causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall. Heart development requires compaction of the ventricular wall into a dense myocardium at mid-gestation. Here, Rhee and colleagues show that the chromatin remodeller Ino80 is critical for the formation of the coronary vasculature, and show that coronary vessels are needed for successful cardiac compaction during embryonic development.
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DOI：
10.1073/pnas.0902408106
发表时间：
2009-09-01
影响因子：
11.1
作者：
Berman, Seth D.;West, Julie C.;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.
影响因子：
4.6
作者：
Chen, Heidi I.;Sharma, Bikram;Red-Horse, Kristy
通讯作者：
Red-Horse, Kristy
影响因子：
64.5
作者：
Morrison, AJ;Highland, J;Shen, XT
通讯作者：
Shen, XT
影响因子：
21.3
作者：
D'Amato G;Luxán G;del Monte-Nieto G;Martínez-Poveda B;Torroja C;Walter W;Bochter MS;Benedito R;Cole S;Martinez F;Hadjantonakis AK;Uemura A;Jiménez-Borreguero LJ;de la Pompa JL
通讯作者：
de la Pompa JL
影响因子：
82.9
作者：
Luxan, Guillermo;Casanova, Jesus C.;Luis de la Pompa, Jose
通讯作者：
Luis de la Pompa, Jose