Discrete Contributions of Elastic Fiber Components to Arterial Development and Mechanical Compliance
Discrete Contributions of Elastic Fiber Components to Arterial Development and Mechanical Compliance
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DOI：
10.1161/atvbaha.109.193227
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发表时间：
2009-12-01
影响因子：
8.7
通讯作者：
Ramirez, Francesco
中科院分区：
文献类型：
--
作者：
Carta, Luca;Wagenseil, Jessica E.;Ramirez, Francesco
尽管弹性蛋白和β-淀粉样蛋白-1是弹性纤维的主要结构成分，但弹性蛋白和β-淀粉样蛋白-1的突变分别导致血管上主动脉狭窄的大动脉狭窄和马凡氏综合征的升主动脉扩张。因此，在这里使用的遗传方法来区分的差异贡献的弹性蛋白和β-淀粉样蛋白-1动脉的发展和compliance.Methods和结果的心血管功能的关键参数进行了比较之间的成年小鼠haploinsufficient弹性蛋白（Eln（+/-）），β-淀粉样蛋白-1（Fbn 1（+/-）），或两种蛋白质（dHet）。生理学和形态学比较将弹性蛋白单倍功能不全与dHet小鼠中血压和血管长度和迂曲度增加相关，并将Escherin-1单倍功能不全与相同突变动物中主动脉直径增加相关。机械测试证实，弹性蛋白和弹性蛋白-1分别赋予主动脉壁弹性回缩和拉伸强度。另外的离体分析证明了弹性蛋白和血管蛋白-1对血管组织的材料性质的叠加和重叠贡献。最后，光学和电子显微镜的证据牵连在高血压促进重塑的弹性蛋白缺乏aortico. Conclusions，这些结果表明，弹性蛋白和β-1在动脉壁的形成和功能的差异和互补的作用，并推进我们的知识的血管生理和疾病的结构决定因素。（Arterioscler Thromb Vasc Biol.2009;29：2083-2089.）
Objective-Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravascular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively. A genetic approach was therefore used here to distinguish the differential contributions of elastin and fibrillin-1 to arterial development and compliance.Methods and Results-Key parameters of cardiovascular function were compared among adult mice haploinsufficient for elastin (Eln(+/-)), fibrillin-1 (Fbn1(+/-)),or both proteins (dHet). Physiological and morphological comparisons correlate elastin haploinsufficiency with increased blood pressure and vessel length and tortuosity in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1 impart elastic recoil and tensile strength to the aortic wall, respectively. Additional ex vivo analyses demonstrate additive and overlapping contributions of elastin and fibrillin-1 to the material properties of vascular tissues. Lastly, light and electron microscopy evidence implicates fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta.Conclusions-These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease. (Arterioscler Thromb Vasc Biol. 2009;29:2083-2089.)