Progressive Microstructural Deterioration Dictates Evolving Biomechanical Dysfunction in the Marfan Aorta.
Progressive Microstructural Deterioration Dictates Evolving Biomechanical Dysfunction in the Marfan Aorta.
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DOI：
10.3389/fcvm.2021.800730
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发表时间：
2021
影响因子：
3.6
通讯作者：
Humphrey JD
中科院分区：
文献类型：
--
作者：
Cavinato C;Chen M;Weiss D;Ruiz-Rodríguez MJ;Schwartz MA;Humphrey JD
导致胸主动脉瘤的中膜恶化由多种原因引起，其中主要是编码β-内酰胺酶-1的基因突变，并导致马凡氏综合征。原纤蛋白-1微纤维与弹性蛋白结合形成弹性纤维，弹性纤维是正常主动脉壁的基本结构、功能和指导成分。受损的弹性纤维不利地影响整体结构完整性并改变平滑肌细胞表型。尽管在表征主动脉粥样硬化蛋白-1相关的动脉粥样硬化病变的临床、组织病理学和机械方面取得了显著进展，但仍然需要在微结构缺陷的进展与决定主动脉功能的相关机械性质之间建立直接相关性。本文选择年龄匹配的野生型、Fbn 1C 1041 G/+和Fbn 1 mgR/mgR小鼠模型来代表马凡氏主动脉表型严重程度增加的三个阶段。离体多光子成像和双轴力学测试的升和降胸主动脉在生理负荷条件下表明，弹性纤维缺陷，胶原纤维重塑，细胞重组增加扩张。三维显微结构表征进一步揭示了中膜退变的径向模式，随着扩张的增加而变得更加均匀，同时与周向材料刚度增加和弹性储能减少密切相关，这两者都包括主动脉功能。
Medial deterioration leading to thoracic aortic aneurysms arises from multiple causes, chief among them mutations to the gene that encodes fibrillin-1 and leads to Marfan syndrome. Fibrillin-1 microfibrils associate with elastin to form elastic fibers, which are essential structural, functional, and instructional components of the normal aortic wall. Compromised elastic fibers adversely impact overall structural integrity and alter smooth muscle cell phenotype. Despite significant progress in characterizing clinical, histopathological, and mechanical aspects of fibrillin-1 related aortopathies, a direct correlation between the progression of microstructural defects and the associated mechanical properties that dictate aortic functionality remains wanting. In this paper, age-matched wild-type, Fbn1C1041G/+, and Fbn1mgR/mgR mouse models were selected to represent three stages of increasing severity of the Marfan aortic phenotype. Ex vivo multiphoton imaging and biaxial mechanical testing of the ascending and descending thoracic aorta under physiological loading conditions demonstrated that elastic fiber defects, collagen fiber remodeling, and cell reorganization increase with increasing dilatation. Three-dimensional microstructural characterization further revealed radial patterns of medial degeneration that become more uniform with increasing dilatation while correlating strongly with increased circumferential material stiffness and decreased elastic energy storage, both of which comprise aortic functionality.
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影响因子：
5.3
作者：
Cavinato C;Murtada SI;Rojas A;Humphrey JD
通讯作者：
Humphrey JD
影响因子：
15.9
作者：
Judge, DP;Biery, NJ;Dietz, HC
通讯作者：
Dietz, HC
影响因子：
3.9
作者：
Bellini, C.;Bersi, M. R.;Humphrey, J. D.
通讯作者：
Humphrey, J. D.
影响因子：
20.1
作者：
Humphrey JD;Schwartz MA;Tellides G;Milewicz DM
通讯作者：
Milewicz DM
DOI：
10.1161/atvbaha.109.193227
发表时间：
2009-12-01
影响因子：
8.7
作者：
Carta, Luca;Wagenseil, Jessica E.;Ramirez, Francesco
通讯作者：
Ramirez, Francesco