Multi-Scale Biomechanical Remodeling in Aging and Genetic Mutant Murine Mitral Valve Leaflets: Insights into Marfan Syndrome
Multi-Scale Biomechanical Remodeling in Aging and Genetic Mutant Murine Mitral Valve Leaflets: Insights into Marfan Syndrome
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DOI：
10.1371/journal.pone.0044639
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发表时间：
2012-09-11
期刊：
影响因子：
3.7
通讯作者：
Butcher, Jonathan
中科院分区：
文献类型：
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作者：
Gould, Russell A.;Sinha, Ravi;Butcher, Jonathan
二尖瓣退行性变是马凡氏综合征病理生理学的关键组成部分。由于在小鼠模型中研究这一点的工具有限，因此对二尖瓣中衰老和基因突变的生物力学后果知之甚少。我们的目的是确定整体生物力学和局部细胞基质变形的关系，在老化和马凡氏相关的Fbn 1突变的小鼠二尖瓣。为了进行这项研究，实施了一种新型拉伸装置和夹持方法，以直接量化小鼠二尖瓣中的整体组织生物力学和局部细胞变形以及基质纤维重新排列。在连续激光光学成像下，对2周龄至10月龄的野生型和Fbn 1突变小鼠的切除二尖瓣瓣叶进行周向检测。小鼠二尖瓣随着年龄的增长而老化，与胶原蛋白分数和基质纤维排列的增加相关。Fbn 1突变导致瓣膜的顺应性显著提高（模量分别为1.34 +/- 0.12和2.51 +/- 0.31 MPa，P
Mitral valve degeneration is a key component of the pathophysiology of Marfan syndrome. The biomechanical consequences of aging and genetic mutation in mitral valves are poorly understood because of limited tools to study this in mouse models. Our aim was to determine the global biomechanical and local cell-matrix deformation relationships in the aging and Marfan related Fbn1 mutated murine mitral valve. To conduct this investigation, a novel stretching apparatus and gripping method was implemented to directly quantify both global tissue biomechanics and local cellular deformation and matrix fiber realignment in murine mitral valves. Excised mitral valve leaflets from wild-type and Fbn1 mutant mice from 2 weeks to 10 months in age were tested in circumferential orientation under continuous laser optical imaging. Mouse mitral valves stiffen with age, correlating with increases in collagen fraction and matrix fiber alignment. Fbn1 mutation resulted in significantly more compliant valves (modulus 1.34 +/- 0.12 vs. 2.51 +/- 0.31 MPa, respectively, P