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

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.