Technical Brief

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

[+] Author and Article Information
Jessica E. Wagenseil

Department of Mechanical Engineering
and Materials Science,
Washington University in St. Louis,
St. Louis, MO 63130
e-mail: jessica.wagenseil@wustl.edu

Manuscript received July 31, 2018; final manuscript received January 28, 2019; published online February 25, 2019. Assoc. Editor: Jonathan Vande Geest.

J Biomech Eng 141(4), 044504 (Feb 25, 2019) (4 pages) Paper No: BIO-18-1348; doi: 10.1115/1.4042766 History: Received July 31, 2018; Revised January 28, 2019

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.

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Grahic Jump Location
Fig. 1

Experimental scaling laws for cardiovascular parameters in maturing mice. Log-log plots and linear regression analyses of cardiovascular parameters versus BW for Eln+/− compared to Eln+/+ (left column) and Fbln5−/− compared to Fbln5+/+ (right column) mice aged 7, 21, and 60 days. ASID (a, b), HW (c, d), SV (e, f), and CO (g, h) are shown. Best fit linear regression equation and R2 are given for each group. * = P < 0.05 for Eln+/− or Fbln5−/− compared to their respective WT control for slope or intercept. Original data are from Le et al. [16,21].



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