Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation
- Publication Type:
- Journal Article
- Citation:
- Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37 (6), pp. 1127 - 1137
- Issue Date:
- 2017-06-01
Closed Access
Filename | Description | Size | |||
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McGrath et al Estrogen Receptor.pdf | Published Version | 1.25 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | McRobb, LS | en_US |
dc.contributor.author |
McGrath, KCY https://orcid.org/0000-0002-6244-3929 |
en_US |
dc.contributor.author | Tsatralis, T | en_US |
dc.contributor.author | Liong, EC | en_US |
dc.contributor.author | Tan, JTM | en_US |
dc.contributor.author | Hughes, G | en_US |
dc.contributor.author | Handelsman, DJ | en_US |
dc.contributor.author | Heather, AK | en_US |
dc.date.available | 2017-04-19 | en_US |
dc.date.issued | 2017-06-01 | en_US |
dc.identifier.citation | Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37 (6), pp. 1127 - 1137 | en_US |
dc.identifier.issn | 1079-5642 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/125940 | |
dc.description.abstract | © 2017 American Heart Association, Inc. Objective-Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro. Approach and Results-Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERβ]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus independently of plaque growth or lipid levels and occurred in association with a site-specific decrease in the proportion of ERβ-positive intimal cells. Calcified lesions expressed collagen I and bone sialoprotein, with decreased matrix Gla protein. In vitro, E2 suppressed ERβ expression and increased VSMC mineralization, demonstrating increased collagen I and II, osteocalcin and bone sialoprotein, and reduced matrix Gla protein and osteopontin. Antagonism or RNA silencing of estrogen receptor alpha, ERβ, or both further increased VSMC mineralization. Conclusions-We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERβ activity. | en_US |
dc.relation.ispartof | Arteriosclerosis, Thrombosis, and Vascular Biology | en_US |
dc.relation.isbasedon | 10.1161/ATVBAHA.117.309054 | en_US |
dc.subject.classification | Cardiovascular System & Hematology | en_US |
dc.subject.mesh | Muscle, Smooth, Vascular | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Myocytes, Smooth Muscle | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Mice, Knockout | en_US |
dc.subject.mesh | Cattle | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Disease Models, Animal | en_US |
dc.subject.mesh | Genetic Predisposition to Disease | en_US |
dc.subject.mesh | Estradiol | en_US |
dc.subject.mesh | Collagen | en_US |
dc.subject.mesh | Apolipoproteins E | en_US |
dc.subject.mesh | Calcium-Binding Proteins | en_US |
dc.subject.mesh | Osteocalcin | en_US |
dc.subject.mesh | Estrogen Receptor alpha | en_US |
dc.subject.mesh | Estrogen Receptor beta | en_US |
dc.subject.mesh | Extracellular Matrix Proteins | en_US |
dc.subject.mesh | Drug Implants | en_US |
dc.subject.mesh | Transfection | en_US |
dc.subject.mesh | Signal Transduction | en_US |
dc.subject.mesh | Cell Differentiation | en_US |
dc.subject.mesh | RNA Interference | en_US |
dc.subject.mesh | Osteogenesis | en_US |
dc.subject.mesh | Phenotype | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Atherosclerosis | en_US |
dc.subject.mesh | Osteopontin | en_US |
dc.subject.mesh | Plaque, Atherosclerotic | en_US |
dc.subject.mesh | Neointima | en_US |
dc.subject.mesh | Integrin-Binding Sialoprotein | en_US |
dc.subject.mesh | Vascular Calcification | en_US |
dc.subject.mesh | Estrogen Receptor Antagonists | en_US |
dc.title | Estrogen Receptor Control of Atherosclerotic Calcification and Smooth Muscle Cell Osteogenic Differentiation | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 6 | en_US |
utslib.citation.volume | 37 | en_US |
utslib.for | 1103 Clinical Sciences | en_US |
utslib.for | 1102 Cardiorespiratory Medicine and Haematology | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
utslib.copyright.status | closed_access | |
pubs.issue | 6 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 37 | en_US |
Abstract:
© 2017 American Heart Association, Inc. Objective-Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro. Approach and Results-Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERβ]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus independently of plaque growth or lipid levels and occurred in association with a site-specific decrease in the proportion of ERβ-positive intimal cells. Calcified lesions expressed collagen I and bone sialoprotein, with decreased matrix Gla protein. In vitro, E2 suppressed ERβ expression and increased VSMC mineralization, demonstrating increased collagen I and II, osteocalcin and bone sialoprotein, and reduced matrix Gla protein and osteopontin. Antagonism or RNA silencing of estrogen receptor alpha, ERβ, or both further increased VSMC mineralization. Conclusions-We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERβ activity.
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