Faculty Collaboration Database

Blood pressure, artery size, and artery compliance parallel bone size and strength in mice with differing ece1 expression. J Biomech Eng 2013 Jun;135(6):61003-9

Date

05/24/2013

Pubmed ID

23699715

Pubmed Central ID

PMC3705900

DOI

10.1115/1.4024161

Scopus ID

2-s2.0-84878075914 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

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.

Author List

Wang Z, Kristianto J, Yen Ooi C, Johnson MG, Litscher SJ, Pugh TD, Sandhu G, Chesler NC, Blank RD

MESH terms used to index this publication - Major topics in bold

Animals
Arteries
Aspartic Acid Endopeptidases
Biomechanical Phenomena
Blood Pressure
Bone and Bones
Compliance
Endothelin-Converting Enzymes
Endothelins
Gene Expression Regulation
Male
Metalloendopeptidases
Mice
Nitric Oxide
Organ Size
RNA, Messenger
Species Specificity