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.

References

1.
West
,
G. B.
,
Brown
,
J. H.
, and
Enquist
,
B. J.
,
1997
, “
A General Model for the Origin of Allometric Scaling Laws in Biology
,”
Science
,
276
(
5309
), pp.
122
126
.
2.
Lindstedt
,
S. L.
, and
Schaeffer
,
P. J.
,
2002
, “
Use of Allometry in Predicting Anatomical and Physiological Parameters of Mammals
,”
Lab. Animals.
,
36
(
1
), pp.
1
19
.
3.
Adolph
,
E. F.
,
1949
, “
Quantitative Relations in the Physiological Constitutions of Mammals
,”
Science
,
109
(
2841
), pp.
579
585
.
4.
Holt
,
J. P.
,
Rhode
,
E. A.
, and
Kines
,
H.
,
1968
, “
Ventricular Volumes and Body Weight in Mammals
,”
Am. J. Physiol.
,
215
(
3
), pp.
704
715
.
5.
Holt
,
J. P.
,
Rhode
,
E. A.
,
Holt
,
W. W.
, and
Kines
,
H.
,
1981
, “
Geometric Similarity of Aorta, Venae Cavae, and Certain of Their Branches in Mammals
,”
Am. J. Physiol.
,
241
(
1
), pp.
R100
R104
.
6.
Stahl
,
W. R.
,
1967
, “
Scaling of Respiratory Variables in Mammals
,”
J. Appl. Physiol.
,
22
(
3
), pp.
453
460
.
7.
Murray
,
C. D.
,
1926
, “
The Physiological Principle of Minimum Work—I: The Vascular System and the Cost of Blood Volume
,”
Proc. Natl. Acad. Sci. U. S. A.
,
12
(
3
), pp.
207
214
.
8.
Sather
,
B. A.
,
Hageman
,
D.
, and
Wagenseil
,
J. E.
,
2012
, “
Murray's Law Holds True in Elastin Haploinsufficient (Eln+/-) and Wild-Type (WT) Mice
,”
ASME J. Biomech. Eng.
,
134
(12), p. 124504.
9.
Wagenseil
,
J. E.
, and
Mecham
,
R. P.
,
2009
, “
Vascular Extracellular Matrix and Arterial Mechanics
,”
Physiol. Rev.
,
89
(
3
), pp.
957
989
.
10.
Dinardo
,
C. L.
,
Venturini
,
G.
,
Zhou
,
E. H.
,
Watanabe
,
I. S.
,
Campos
,
L. C.
,
Dariolli
,
R.
,
da Motta-Leal-Filho
,
J. M.
,
Carvalho
,
V. M.
,
Cardozo
,
K. H.
,
Krieger
,
J. E.
,
Alencar
,
A. M.
, and
Pereira
,
A. C.
,
2014
, “
Variation of Mechanical Properties and Quantitative Proteomics of VSMC Along the Arterial Tree
,”
Am. J. Physiol. Heart Circ. Physiol.
,
306
(
4
), pp.
H505
H516
.
11.
Wagenseil
,
J. E.
,
Nerurkar
,
N. L.
,
Knutsen
,
R. H.
,
Okamoto
,
R. J.
,
Li
,
D. Y.
, and
Mecham
,
R. P.
,
2005
, “
Effects of Elastin Haploinsufficiency on the Mechanical Behavior of Mouse Arteries
,”
Am. J. Physiol. Heart Circ. Physiol.
,
289
(
3
), pp.
H1209
H1217
.
12.
Le
,
V. P.
,
Cheng
,
J. K.
,
Kim
,
J.
,
Staiculescu
,
M. C.
,
Ficker
,
S. W.
,
Sheth
,
S. C.
,
Bhayani
,
S. A.
,
Mecham
,
R. P.
,
Yanagisawa
,
H.
, and
Wagenseil
,
J. E.
,
2015
, “
Mechanical Factors Direct Mouse Aortic Remodelling During Early Maturation
,”
J. R. Soc. Interface.
,
12
(
104
), p.
20141350
.
13.
Li
,
D. Y.
,
Toland
,
A. E.
,
Boak
,
B. B.
,
Atkinson
,
D. L.
,
Ensing
,
G. J.
,
Morris
,
C. A.
, and Keating, M. T.,
1997
, “
Elastin Point Mutations Cause an Obstructive Vascular Disease, Supravalvular Aortic Stenosis
,”
Hum. Mol. Genet.
,
6
(
7
), pp.
1021
1028
.
14.
Loeys
,
B.
,
Van Maldergem
,
L.
,
Mortier
,
G.
,
Coucke
,
P.
,
Gerniers
,
S.
,
Naeyaert
,
J. M.
, and De Paepe, A.,
2002
, “
Homozygosity for a Missense Mutation in Fibulin-5 (FBLN5) Results in a Severe Form of Cutis Laxa
,”
Hum. Mol. Genet.
,
11
(
18
), pp.
2113
2118
.
15.
Le
,
V. P.
,
Knutsen
,
R. H.
,
Mecham
,
R. P.
, and
Wagenseil
,
J. E.
,
2011
, “
Decreased Aortic Diameter and Compliance Precedes Blood Pressure Increases in Postnatal Development of Elastin-Insufficient Mice
,”
Am. J. Physiol. Heart Circ. Physiol.
,
301
(
1
), pp.
H221
H229
.
16.
Le
,
V. P.
,
Stoka
,
K. V.
,
Yanagisawa
,
H.
, and
Wagenseil
,
J. E.
,
2014
, “
Fibulin‐5 Null Mice With Decreased Arterial Compliance Maintain Normal Systolic Left Ventricular Function, But Not Diastolic Function During Maturation
,”
Physiol. Rep.
,
2
(
3
), p. e00257.
17.
Wan
,
W.
,
Yanagisawa
,
H.
, and
Gleason
,
R. L.
, Jr.
,
2010
, “
Biomechanical and Microstructural Properties of Common Carotid Arteries From Fibulin-5 Null Mice
,”
Ann. Biomed. Eng.
,
38
(
12
), pp.
3605
3617
.
18.
Kozel
,
B. A.
,
Danback
,
J. R.
,
Waxler
,
J. L.
,
Knutsen
,
R. H.
,
de Las Fuentes
,
L.
,
Reusz
,
G. S.
,
Kis
,
E.
,
Bhatt
,
A. B.
, and
Pober
,
B. R.
,
2014
, “
Williams Syndrome Predisposes to Vascular Stiffness Modified by Antihypertensive Use and Copy Number Changes in NCF1
,”
Hypertension
,
63
(
1
), pp.
74
79
.
19.
Papke
,
C. L.
, and
Yanagisawa
,
H.
,
2014
, “
Fibulin-4 and Fibulin-5 in Elastogenesis and Beyond: Insights From Mouse and Human Studies
,”
Matrix Biol.
,
37
, pp.
142
149
.
20.
Mitchell
,
G. F.
,
Hwang
,
S. J.
,
Vasan
,
R. S.
,
Larson
,
M. G.
,
Pencina
,
M. J.
,
Hamburg
,
N. M.
,
Vita
,
J. A.
,
Levy
,
D.
, and
Benjamin
,
E. J.
,
2010
, “
Arterial Stiffness and Cardiovascular Events: The Framingham Heart Study
,”
Circulation
,
121
(
4
), pp.
505
511
.
21.
Le
,
V. P.
, and
Wagenseil
,
J. E.
,
2012
, “
Echocardiographic Characterization of Postnatal Development in Mice With Reduced Arterial Elasticity
,”
Cardiovasc. Eng. Technol.
,
3
(
4
), pp.
424
438
.
22.
Li
,
D. Y.
,
Faury
,
G.
,
Taylor
,
D. G.
,
Davis
,
E. C.
,
Boyle
,
W. A.
,
Mecham
,
R. P.
,
Stenzel
,
P.
,
Boak
,
B.
, and
Keating
,
M. T.
,
1998
, “
Novel Arterial Pathology in Mice and Humans Hemizygous for Elastin
,”
J. Clin. Invest.
,
102
(
10
), pp.
1783
1787
.
23.
Yanagisawa
,
H.
,
Davis
,
E. C.
,
Starcher
,
B. C.
,
Ouchi
,
T.
,
Yanagisawa
,
M.
,
Richardson
,
J. A.
, and Olson, E. N.,
2002
, “
Fibulin-5 Is an Elastin-Binding Protein Essential for Elastic Fibre Development In Vivo
,”
Nature
,
415
(
6868
), pp.
168
171
.
24.
Dawson
,
T.
,
2014
, “
Allometric Relations and Scaling Laws for the Cardiovascular System of Mammals
,”
System
,
2
(
2
), pp.
168
185
.
25.
Feldman
,
H. A.
, and
McMahon
,
T. A.
,
1983
, “
The 3/4 Mass Exponent for Energy Metabolism Is Not a Statistical Artifact
,”
Respir. Physiol.
,
52
(
2
), pp.
149
163
.
26.
Faury
,
G.
,
Pezet
,
M.
,
Knutsen
,
R. H.
,
Boyle
,
W. A.
,
Heximer
,
S. P.
,
McLean
,
S. E.
,
Minkes
,
R. K.
,
Blumer
,
K. J.
,
Kovacs
,
A.
,
Kelly
,
D. P.
,
Li
,
D. Y.
,
Starcher
,
B.
, and
Mecham
,
R. P.
,
2003
, “
Developmental Adaptation of the Mouse Cardiovascular System to Elastin Haploinsufficiency
,”
J. Clin. Invest.
,
112
(
9
), pp.
1419
1428
.
27.
Wagenseil
,
J. E.
,
Ciliberto
,
C. H.
,
Knutsen
,
R. H.
,
Levy
,
M. A.
,
Kovacs
,
A.
, and
Mecham
,
R. P.
,
2010
, “
The Importance of Elastin to Aortic Development in Mice
,”
Am. J. Physiol. Heart Circ. Physiol.
,
299
(
2
), pp.
H257
H264
.
28.
Bellini
,
C.
,
Bersi
,
M. R.
,
Caulk
,
A. W.
,
Ferruzzi
,
J.
,
Milewicz
,
D. M.
,
Ramirez
,
F.
,
Rifkin
,
D. B.
,
Tellides
,
G.
,
Yanagisawa
,
H.
, and
Humphrey
,
J. D.
,
2017
, “
Comparison of 10 Murine Models Reveals a Distinct Biomechanical Phenotype in Thoracic Aortic Aneurysms
,”
J. R. Soc. Interface
,
14
(
130
), p. 20161036.
29.
O'Rourke
,
M. F.
,
Staessen
,
J. A.
,
Vlachopoulos
,
C.
,
Duprez
,
D.
, and
Plante
,
G. E.
,
2002
, “
Clinical Applications of Arterial Stiffness; Definitions and Reference Values
,”
Am. J. Hypertens.
,
15
(
5
), pp.
426
444
.
30.
Dewey
,
F. E.
,
Rosenthal
,
D.
,
Murphy
,
D. J.
, Jr.
,
Froelicher
,
V. F.
, and
Ashley
,
E. A.
,
2008
, “
Does Size Matter? Clinical Applications of Scaling Cardiac Size and Function for Body Size
,”
Circulation
,
117
(
17
), pp.
2279
2287
.
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