The recombinant congenic mouse strains HcB-8 and HcB-23 differ in femoral shape, size, and strength, with HcB-8 femora being more gracile, more cylindrical, weaker, and having higher Young's modulus. In previous work, we mapped a robust, pleiotropic quantitative trait locus for these bone traits. Ece1, encoding endothelin converting enzyme 1, is a positional candidate gene for this locus, and was less expressed in HcB-8 bone. We hypothesized that the same genetic factors would impose analogous developmental trajectories on arteries to those in bones. Cardiovascular hemodynamics and biomechanics of carotids were measured in adult HcB-8 and HcB-23 mice. Biological differences in heart and arteries were examined at mRNA and protein levels. As in bone, Ece1 expression was higher in HcB-23 heart and arteries (p < 0.05), and its expression was correlated with that of the endothelin B type receptor target Nos3, encoding endothelial nitric oxide synthase. HcB-8 mice had higher ambulatory blood pressure (p < 0.005) than HcB-23 mice. Ex vivo, at identical pressures, HcB-8 carotid arteries had smaller diameters and lower compliance (p < 0.05), but the same elastic modulus compared to HcB-23 carotid arteries. HcB-8 hearts were heavier than HcB-23 hearts (p < 0.01). HcB-8 has both small, stiff bones and small, stiff arteries, lower expression of Ece1 and Nos3, associated in each case with less favorable function. These findings suggest that endothelin signaling could serve as a nexus for the convergence of skeletal and vascular modeling, providing a potential mechanism for the epidemiologic association between skeletal fragility and atherosclerosis.
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June 2013
Research-Article
Blood Pressure, Artery Size, and Artery Compliance Parallel Bone Size and Strength in Mice With Differing Ece1 Expression
Zhijie Wang,
Zhijie Wang
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison, WI 53706
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison, WI 53706
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Jasmin Kristianto,
Jasmin Kristianto
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
Endocrine and Reproductive Physiology Program,
1465 MSC, 1300 University Avenue,
Madison,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
53705;Endocrine and Reproductive Physiology Program,
University of Wisconsin
,1465 MSC, 1300 University Avenue,
Madison,
WI
53706
Search for other works by this author on:
Chen Yen Ooi,
Chen Yen Ooi
1
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison,
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison,
WI
537061Present address: Bioengineering Office, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK.
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Gurpreet Sandhu,
Gurpreet Sandhu
2
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
537052Present address: Faculty of Medicine, St. Martinus University, Brionplein 1, Otrobanda, P.O. Box 2050, Curaçao.
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Naomi C. Chesler,
Naomi C. Chesler
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison,
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison,
WI
53706
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Robert D. Blank
Robert D. Blank
3
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
Endocrine and Reproductive Physiology Program,
1465 MSC, 1300 University Avenue,
Madison,
e-mail: rdb@medicine.wisc.edu
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
53705;Endocrine and Reproductive Physiology Program,
University of Wisconsin
,1465 MSC, 1300 University Avenue,
Madison,
WI
53706e-mail: rdb@medicine.wisc.edu
3Corresponding author.
Search for other works by this author on:
Zhijie Wang
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison, WI 53706
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison, WI 53706
Jasmin Kristianto
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
Endocrine and Reproductive Physiology Program,
1465 MSC, 1300 University Avenue,
Madison,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
53705;Endocrine and Reproductive Physiology Program,
University of Wisconsin
,1465 MSC, 1300 University Avenue,
Madison,
WI
53706
Chen Yen Ooi
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison,
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison,
WI
53706
Gurpreet Sandhu
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
53705
Naomi C. Chesler
Department of Biomedical Engineering,
2146 ECB, 1550 Engineering Drive,
Madison,
University of Wisconsin
,2146 ECB, 1550 Engineering Drive,
Madison,
WI
53706
Robert D. Blank
Geriatrics Research, Education, and Clinical Center,
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
Division of Endocrinology,
Department of Medicine,
4148 MFCB (5148), 1685 Highland Avenue,
Madison,
Endocrine and Reproductive Physiology Program,
1465 MSC, 1300 University Avenue,
Madison,
e-mail: rdb@medicine.wisc.edu
William S. Middleton Veterans Hospital,
2500 Overlook Terrace,
Madison,
WI
53705;Division of Endocrinology,
Department of Medicine,
University of Wisconsin
,4148 MFCB (5148), 1685 Highland Avenue,
Madison,
WI
53705;Endocrine and Reproductive Physiology Program,
University of Wisconsin
,1465 MSC, 1300 University Avenue,
Madison,
WI
53706e-mail: rdb@medicine.wisc.edu
1Present address: Bioengineering Office, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK.
2Present address: Faculty of Medicine, St. Martinus University, Brionplein 1, Otrobanda, P.O. Box 2050, Curaçao.
3Corresponding author.
Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received June 26, 2012; final manuscript received December 21, 2012; accepted manuscript posted April 8, 2013; published online May 9, 2013. Assoc. Editor: Hai-Chao Han.
J Biomech Eng. Jun 2013, 135(6): 061003 (9 pages)
Published Online: May 9, 2013
Article history
Received:
June 26, 2012
Revision Received:
December 21, 2012
Accepted:
April 8, 2013
Citation
Wang, Z., Kristianto, J., Yen Ooi, C., Johnson, M. G., Litscher, S. J., Pugh, T. D., Sandhu, G., Chesler, N. C., and Blank, R. D. (May 9, 2013). "Blood Pressure, Artery Size, and Artery Compliance Parallel Bone Size and Strength in Mice With Differing Ece1 Expression." ASME. J Biomech Eng. June 2013; 135(6): 061003. https://doi.org/10.1115/1.4024161
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