The importance of elastin to aortic development in mice.
The importance of elastin to aortic development in mice.
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DOI：
10.1152/ajpheart.00194.2010
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发表时间：
2010-08
期刊：
影响因子：
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通讯作者：
Jessica E. Wagenseil;Christopher H. Ciliberto;Russell H Knutsen;M. Levy;A. Kovács;R. Mecham
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文献类型：
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作者：
Jessica E. Wagenseil;Christopher H. Ciliberto;Russell H Knutsen;M. Levy;A. Kovács;R. Mecham
弹性蛋白是脊椎动物动脉的重要组成部分，在心动周期中提供弹性并储存能量。动脉壁中弹性蛋白的产生始于妊娠中期，但在人类和小鼠发育的最后三分之一期间迅速增加，就像血压和心输出量急剧增加一样。本研究的目的是表征弹性蛋白水平降低的动脉发育的结构、血液动力学和力学，并确定脊椎动物心血管系统中需要弹性蛋白的关键时间段。缺乏弹性蛋白（Eln（-/-））或具有约一半正常水平（Eln（+/-））的小鼠显示相对正常的心血管发育，直至胚胎第（E）18天，如通过动脉形态、左心室血压和心脏功能所评估的。先前的研究表明，仅仅几天后，在出生时，Eln（-/-）小鼠死于高血压和扭曲狭窄的动脉。在E18到出生的这段时间里，Eln（+/-）小鼠的血管壁增加了额外的平滑肌细胞层，平均血压比野生型动物高25%。这些发现表明，弹性蛋白仅在胚胎发育的最后几天开始对小鼠的正常心血管结构和功能是必需的。在此期间血压的大幅增加可能会将血液动力学力推过临界阈值，在该临界阈值处，心血管功能需要弹性蛋白。了解弹性蛋白量和血管发育中的血流动力学之间的相互作用将有助于设计人类弹性蛋白病的治疗方法，并优化组织工程的方案。
Elastin is an essential component of vertebrate arteries that provides elasticity and stores energy during the cardiac cycle. Elastin production in the arterial wall begins midgestation but increases rapidly during the last third of human and mouse development, just as blood pressure and cardiac output increase sharply. The aim of this study is to characterize the structure, hemodynamics, and mechanics of developing arteries with reduced elastin levels and determine the critical time period where elastin is required in the vertebrate cardiovascular system. Mice that lack elastin (Eln(-/-)) or have approximately one-half the normal level (Eln(+/-)) show relatively normal cardiovascular development up to embryonic day (E) 18 as assessed by arterial morphology, left ventricular blood pressure, and cardiac function. Previous work showed that just a few days later, at birth, Eln(-/-) mice die with high blood pressure and tortuous, stenotic arteries. During this period from E18 to birth, Eln(+/-) mice add extra layers of smooth muscle cells to the vessel wall and have a mean blood pressure 25% higher than wild-type animals. These findings demonstrate that elastin is only necessary for normal cardiovascular structure and function in mice starting in the last few days of fetal development. The large increases in blood pressure during this period may push hemodynamic forces over a critical threshold where elastin becomes required for cardiovascular function. Understanding the interplay between elastin amounts and hemodynamic forces in developing vessels will help design treatments for human elastinopathies and optimize protocols for tissue engineering.