Increased Hemodynamic Load in Early Embryonic Stages Alters Myofibril and Mitochondrial Organization in the Myocardium.
Increased Hemodynamic Load in Early Embryonic Stages Alters Myofibril and Mitochondrial Organization in the Myocardium.
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DOI：
10.3389/fphys.2017.00631
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发表时间：
2017
影响因子：
4
通讯作者：
Rugonyi S
中科院分区：
文献类型：
--
作者：
Midgett M;López CS;David L;Maloyan A;Rugonyi S
正常的血流对于胚胎发育过程中心脏的正常形成至关重要，因为异常的血流动力学负荷（血压和剪切应力）会导致先天性心脏病 (CHD) 中出现的心脏缺陷。然而，血流改变与心脏畸形和缺陷相关的有害重塑过程仍不清楚。心脏发育是一个精心策划的过程，在组织、细胞和亚细胞水平上发生快速转变。在整个发育过程中，随着血流动力学负荷的增加，心肌细胞通过在拉伸方向上排列并增加收缩单位的数量，在心脏组织成熟中发挥重要作用。这项研究阐明了血流改变对体内流出道心肌中肌原纤维和线粒体构型的早期影响。流出道束带用于增加汉堡和汉密尔顿阶段 18 和 24 之间鸡胚心脏的血流动力学负荷（管状心脏阶段约 24 小时）。 3D 聚焦离子束扫描电子显微镜分析确定，血流动力学负荷的增加会引起发育中心肌的变化，其特征是更厚的肌原纤维束在圆周方向上分布更多，线粒体在细胞核周围组织成大簇。蛋白质组质谱分析量化了条带后蛋白质组成的改变，这与肌原纤维细丝组装和功能的改变以及线粒体的维持和组织一致。此外，蛋白质组数据的通路分析确定了响应条带的信号通路可能的激活，包括肾素-血管紧张素系统（RAS）。成像和蛋白质组数据相结合表明，早期胚胎阶段的肌原纤维和线粒体排列是一个关键的发育过程，当受到血流改变的干扰时，可能会导致心脏畸形和缺陷。
Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease (CHD). However, the detrimental remodeling processes that relate altered blood flow to cardiac malformation and defects remain unclear. Heart development is a finely orchestrated process with rapid transformations that occur at the tissue, cell, and subcellular levels. Myocardial cells play an essential role in cardiac tissue maturation by aligning in the direction of stretch and increasing the number of contractile units as hemodynamic load increases throughout development. This study elucidates the early effects of altered blood flow on myofibril and mitochondrial configuration in the outflow tract myocardium in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24 (~24 h during tubular heart stages). 3D focused ion beam scanning electron microscopy analysis determined that increased hemodynamic load induced changes in the developing myocardium, characterized by thicker myofibril bundles that were more disbursed in circumferential orientation, and mitochondria that organized in large clusters around the nucleus. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with altered myofibril thin filament assembly and function, and mitochondrial maintenance and organization. Additionally, pathway analysis of the proteomics data identified possible activation of signaling pathways in response to banding, including the renin-angiotensin system (RAS). Imaging and proteomic data combined indicate that myofibril and mitochondrial arrangement in early embryonic stages is a critical developmental process that when disturbed by altered blood flow may contribute to cardiac malformation and defects.
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影响因子：
3.7
作者：
Liu A;Yin X;Shi L;Li P;Thornburg KL;Wang R;Rugonyi S
通讯作者：
Rugonyi S
DOI：
10.1111/j.1549-8719.2010.00025.x
发表时间：
2010-04
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Culver JC;Dickinson ME
通讯作者：
Dickinson ME
DOI：
10.1083/jcb.201403129
发表时间：
2014-10-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gao J;Schatton D;Martinelli P;Hansen H;Pla-Martin D;Barth E;Becker C;Altmueller J;Frommolt P;Sardiello M;Rugarli EI
通讯作者：
Rugarli EI
DOI：
10.1016/s0022-2828(08)80026-0
发表时间：
1995-01-01
影响因子：
5
作者：
BEINLICH, CJ;RISSINGER, CJ;MORGAN, HE
通讯作者：
MORGAN, HE
DOI：
10.1002/ar.20885
发表时间：
2009-05-01
影响因子：
2
作者：
Hu, Norman;Christensen, Douglas A.;Hawkins, John A.
通讯作者：
Hawkins, John A.