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动脉弹性纤维数量减少或完整性受损会改变成熟小鼠主动脉直径和心脏重量的异速生长比例关系,但不会影响心脏功能。

Reduced Amount or Integrity of Arterial Elastic Fibers Alters Allometric Scaling Relationships for Aortic Diameter and Heart Weight, But Not Cardiac Function in Maturing Mice.

作者信息

Wagenseil Jessica E

机构信息

Department of Mechanical Engineeringand Materials Science,Washington University in St. Louis,St. Louis, MO 63130e-mail:

出版信息

J Biomech Eng. 2019 Apr 1;141(4):0445041-4. doi: 10.1115/1.4042766.

Abstract

Allometric scaling laws relate physiologic parameters to body weight. Genetically modified mice allow investigation of allometric scaling laws when fundamental cardiovascular components are altered. Elastin haploinsufficient (Eln+/-) mice have reduced elastin amounts, and fibulin-5 knockout (Fbln5-/-) mice have compromised elastic fiber integrity in the large arteries which may alter cardiovascular scaling laws. Previously published echocardiography data used to investigate aortic and left ventricular function in Eln+/- and Fbln5-/- mice throughout postnatal development and early adulthood were reanalyzed to determine cardiovascular scaling laws. Aortic diameter, heart weight, stroke volume, and cardiac output have scaling exponents within 1-32% of the predicted theoretical range, indicating that the scaling laws apply to maturing mice. For aortic diameter, Eln+/- and Eln+/+ mice have similar scaling exponents, but different scaling constants, suggesting a shift in starting diameter, but no changes in aortic growth with body weight. In contrast, the scaling exponent for aortic diameter in Fbln5-/- mice is lower than Fbln5+/+ mice, but the scaling constant is similar, suggesting that aortic growth with body weight is compromised in Fbln5-/- mice. For both Eln+/- and Fbln5-/- groups, the scaling constant for heart weight is increased compared to the respective control group, suggesting an increase in starting heart weight, but no change in the increase with body weight during maturation. The scaling exponents and constants for stroke volume and cardiac output are not significantly affected by reduced elastin amounts or compromised elastic fiber integrity in the large arteries, highlighting a robust cardiac adaptation despite arterial defects.

摘要

异速生长比例定律将生理参数与体重联系起来。基因改造小鼠可用于研究当基本心血管成分发生改变时的异速生长比例定律。弹性蛋白单倍体不足(Eln+/-)小鼠的弹性蛋白量减少,而纤维连接蛋白5基因敲除(Fbln5-/-)小鼠的大动脉弹性纤维完整性受损,这可能会改变心血管比例定律。对先前发表的用于研究Eln+/-和Fbln5-/-小鼠在整个出生后发育和成年早期的主动脉和左心室功能的超声心动图数据进行重新分析,以确定心血管比例定律。主动脉直径、心脏重量、每搏输出量和心输出量的比例指数在预测理论范围的1-32%以内,表明该比例定律适用于成熟小鼠。对于主动脉直径,Eln+/-和Eln+/+小鼠具有相似的比例指数,但比例常数不同,这表明起始直径发生了变化,但主动脉随体重的生长没有变化。相比之下,Fbln5-/-小鼠的主动脉直径比例指数低于Fbln5+/+小鼠,但比例常数相似,这表明Fbln5-/-小鼠中主动脉随体重的生长受到损害。对于Eln+/-和Fbln5-/-两组,与各自的对照组相比,心脏重量的比例常数增加,这表明起始心脏重量增加,但在成熟过程中随体重增加的情况没有变化。每搏输出量和心输出量的比例指数和常数不受弹性蛋白量减少或大动脉弹性纤维完整性受损的显著影响,这突出表明尽管存在动脉缺陷,但心脏具有强大的适应性。

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