Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice

ABSTRACT Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP‐deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP‐deficient (Mgp–/–) mice show progressive deposition of hydroxyapatite...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of bone and mineral research 2014-02, Vol.29 (2), p.327-337
Hauptverfasser: Khavandgar, Zohreh, Roman, Hassem, Li, Jingjing, Lee, Sara, Vali, Hojatollah, Brinckmann, Juergen, Davis, Elaine C, Murshed, Monzur
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 337
container_issue 2
container_start_page 327
container_title Journal of bone and mineral research
container_volume 29
creator Khavandgar, Zohreh
Roman, Hassem
Li, Jingjing
Lee, Sara
Vali, Hojatollah
Brinckmann, Juergen
Davis, Elaine C
Murshed, Monzur
description ABSTRACT Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP‐deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP‐deficient (Mgp–/–) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age. The mechanism of antimineralization function of MGP is not fully understood. We examined the progression of vascular calcification and expression of several chondrogenic/osteogenic markers in the thoracic aortas of Mgp–/– mice at various ages. Although cells with chondrocyte‐like morphology have been reported in the calcified aorta, our gene expression data indicate that chondrogenic/osteogenic markers are not upregulated in the arteries prior to the initiation of calcification. Interestingly, arterial calcification in Mgp–/– mice appears first in the elastic laminae. Considering the known mineral scaffolding function of elastin (ELN), a major elastic lamina protein, we hypothesize that elastin content in the laminae is a critical determinant for arterial calcification in Mgp–/– mice. To investigate this, we performed micro–computed tomography (µCT) and histological analyses of the aortas of Mgp–/–;Eln+/– mice and show that elastin haploinsufficiency significantly reduces arterial calcification in this strain. Our data suggest that MGP deficiency leads to alterations of vascular ECM that may in turn initiate arterial calcification. © 2014 American Society for Bone and Mineral Research.
doi_str_mv 10.1002/jbmr.2039
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1490900425</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3184307651</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4549-20424f32eb278b5de2696bfa5ae581f1340fe037f0f02586bddfab985cc679953</originalsourceid><addsrcrecordid>eNp1kMtO3DAUQC1EBVNgwQ-gSGxgkZnrV-IsYUoHKkYgBOvIca6LR3kMdqJqdnxCv7Ff0qQzdFGpKy_uuedah5BTClMKwGarovZTBjzbIxMqGY9Foug-mYBSIgbB6SH5HMIKABKZJAfkkHEl01SyCSlvKh0610S3el21rgm9tc44bMwmuqvXWGKIuleMHn373WMIrm2i1kZXvkPvdBXNdWXcsKG7cTJ4lovHX-8_v-DW0kVLZ_CYfLK6Cniye4_Iy9eb5_ltfP-wuJtf3cdGSJHFDAQTljMsWKoKWSJLsqSwWmqUilrKBVgEnlqwwKRKirK0usiUNCZJs0zyI3Kx9a59-9Zj6PLaBYNVpRts-5BTkUEGw5URPf8HXbW9b4bfDVSqgDIp-EBdbinj2xA82nztXa39JqeQj-nzMX0-ph_Ys52xL2os_5IfrQdgtgV-uAo3_zfl366XT3-UvwGfL45q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1478012543</pqid></control><display><type>article</type><title>Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Khavandgar, Zohreh ; Roman, Hassem ; Li, Jingjing ; Lee, Sara ; Vali, Hojatollah ; Brinckmann, Juergen ; Davis, Elaine C ; Murshed, Monzur</creator><creatorcontrib>Khavandgar, Zohreh ; Roman, Hassem ; Li, Jingjing ; Lee, Sara ; Vali, Hojatollah ; Brinckmann, Juergen ; Davis, Elaine C ; Murshed, Monzur</creatorcontrib><description>ABSTRACT Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP‐deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP‐deficient (Mgp–/–) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age. The mechanism of antimineralization function of MGP is not fully understood. We examined the progression of vascular calcification and expression of several chondrogenic/osteogenic markers in the thoracic aortas of Mgp–/– mice at various ages. Although cells with chondrocyte‐like morphology have been reported in the calcified aorta, our gene expression data indicate that chondrogenic/osteogenic markers are not upregulated in the arteries prior to the initiation of calcification. Interestingly, arterial calcification in Mgp–/– mice appears first in the elastic laminae. Considering the known mineral scaffolding function of elastin (ELN), a major elastic lamina protein, we hypothesize that elastin content in the laminae is a critical determinant for arterial calcification in Mgp–/– mice. To investigate this, we performed micro–computed tomography (µCT) and histological analyses of the aortas of Mgp–/–;Eln+/– mice and show that elastin haploinsufficiency significantly reduces arterial calcification in this strain. Our data suggest that MGP deficiency leads to alterations of vascular ECM that may in turn initiate arterial calcification. © 2014 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.2039</identifier><identifier>PMID: 23857752</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aging - genetics ; Aging - metabolism ; Aging - pathology ; Animals ; Antigens, Differentiation - genetics ; Antigens, Differentiation - metabolism ; Aorta, Thoracic - diagnostic imaging ; Aorta, Thoracic - metabolism ; Aorta, Thoracic - pathology ; Aorta, Thoracic - physiopathology ; Durapatite - metabolism ; ELASTIN ; Elastin - genetics ; Elastin - metabolism ; KEUTEL SYNDROME ; MATRIX GLA PROTEIN ; Mice ; Mice, Knockout ; Proteins - genetics ; Proteins - metabolism ; VASCULAR CALCIFICATION ; Vascular Calcification - diagnostic imaging ; Vascular Calcification - genetics ; Vascular Calcification - metabolism ; Vascular Calcification - pathology ; Vascular Calcification - physiopathology ; VASCULAR SMOOTH MUSCLE CELLS ; X-Ray Microtomography</subject><ispartof>Journal of bone and mineral research, 2014-02, Vol.29 (2), p.327-337</ispartof><rights>2014 American Society for Bone and Mineral Research</rights><rights>2014 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4549-20424f32eb278b5de2696bfa5ae581f1340fe037f0f02586bddfab985cc679953</citedby><cites>FETCH-LOGICAL-c4549-20424f32eb278b5de2696bfa5ae581f1340fe037f0f02586bddfab985cc679953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.2039$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.2039$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23857752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khavandgar, Zohreh</creatorcontrib><creatorcontrib>Roman, Hassem</creatorcontrib><creatorcontrib>Li, Jingjing</creatorcontrib><creatorcontrib>Lee, Sara</creatorcontrib><creatorcontrib>Vali, Hojatollah</creatorcontrib><creatorcontrib>Brinckmann, Juergen</creatorcontrib><creatorcontrib>Davis, Elaine C</creatorcontrib><creatorcontrib>Murshed, Monzur</creatorcontrib><title>Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP‐deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP‐deficient (Mgp–/–) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age. The mechanism of antimineralization function of MGP is not fully understood. We examined the progression of vascular calcification and expression of several chondrogenic/osteogenic markers in the thoracic aortas of Mgp–/– mice at various ages. Although cells with chondrocyte‐like morphology have been reported in the calcified aorta, our gene expression data indicate that chondrogenic/osteogenic markers are not upregulated in the arteries prior to the initiation of calcification. Interestingly, arterial calcification in Mgp–/– mice appears first in the elastic laminae. Considering the known mineral scaffolding function of elastin (ELN), a major elastic lamina protein, we hypothesize that elastin content in the laminae is a critical determinant for arterial calcification in Mgp–/– mice. To investigate this, we performed micro–computed tomography (µCT) and histological analyses of the aortas of Mgp–/–;Eln+/– mice and show that elastin haploinsufficiency significantly reduces arterial calcification in this strain. Our data suggest that MGP deficiency leads to alterations of vascular ECM that may in turn initiate arterial calcification. © 2014 American Society for Bone and Mineral Research.</description><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>Aging - pathology</subject><subject>Animals</subject><subject>Antigens, Differentiation - genetics</subject><subject>Antigens, Differentiation - metabolism</subject><subject>Aorta, Thoracic - diagnostic imaging</subject><subject>Aorta, Thoracic - metabolism</subject><subject>Aorta, Thoracic - pathology</subject><subject>Aorta, Thoracic - physiopathology</subject><subject>Durapatite - metabolism</subject><subject>ELASTIN</subject><subject>Elastin - genetics</subject><subject>Elastin - metabolism</subject><subject>KEUTEL SYNDROME</subject><subject>MATRIX GLA PROTEIN</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>VASCULAR CALCIFICATION</subject><subject>Vascular Calcification - diagnostic imaging</subject><subject>Vascular Calcification - genetics</subject><subject>Vascular Calcification - metabolism</subject><subject>Vascular Calcification - pathology</subject><subject>Vascular Calcification - physiopathology</subject><subject>VASCULAR SMOOTH MUSCLE CELLS</subject><subject>X-Ray Microtomography</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtO3DAUQC1EBVNgwQ-gSGxgkZnrV-IsYUoHKkYgBOvIca6LR3kMdqJqdnxCv7Ff0qQzdFGpKy_uuedah5BTClMKwGarovZTBjzbIxMqGY9Foug-mYBSIgbB6SH5HMIKABKZJAfkkHEl01SyCSlvKh0610S3el21rgm9tc44bMwmuqvXWGKIuleMHn373WMIrm2i1kZXvkPvdBXNdWXcsKG7cTJ4lovHX-8_v-DW0kVLZ_CYfLK6Cniye4_Iy9eb5_ltfP-wuJtf3cdGSJHFDAQTljMsWKoKWSJLsqSwWmqUilrKBVgEnlqwwKRKirK0usiUNCZJs0zyI3Kx9a59-9Zj6PLaBYNVpRts-5BTkUEGw5URPf8HXbW9b4bfDVSqgDIp-EBdbinj2xA82nztXa39JqeQj-nzMX0-ph_Ys52xL2os_5IfrQdgtgV-uAo3_zfl366XT3-UvwGfL45q</recordid><startdate>201402</startdate><enddate>201402</enddate><creator>Khavandgar, Zohreh</creator><creator>Roman, Hassem</creator><creator>Li, Jingjing</creator><creator>Lee, Sara</creator><creator>Vali, Hojatollah</creator><creator>Brinckmann, Juergen</creator><creator>Davis, Elaine C</creator><creator>Murshed, Monzur</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TS</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201402</creationdate><title>Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice</title><author>Khavandgar, Zohreh ; Roman, Hassem ; Li, Jingjing ; Lee, Sara ; Vali, Hojatollah ; Brinckmann, Juergen ; Davis, Elaine C ; Murshed, Monzur</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4549-20424f32eb278b5de2696bfa5ae581f1340fe037f0f02586bddfab985cc679953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aging - genetics</topic><topic>Aging - metabolism</topic><topic>Aging - pathology</topic><topic>Animals</topic><topic>Antigens, Differentiation - genetics</topic><topic>Antigens, Differentiation - metabolism</topic><topic>Aorta, Thoracic - diagnostic imaging</topic><topic>Aorta, Thoracic - metabolism</topic><topic>Aorta, Thoracic - pathology</topic><topic>Aorta, Thoracic - physiopathology</topic><topic>Durapatite - metabolism</topic><topic>ELASTIN</topic><topic>Elastin - genetics</topic><topic>Elastin - metabolism</topic><topic>KEUTEL SYNDROME</topic><topic>MATRIX GLA PROTEIN</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>VASCULAR CALCIFICATION</topic><topic>Vascular Calcification - diagnostic imaging</topic><topic>Vascular Calcification - genetics</topic><topic>Vascular Calcification - metabolism</topic><topic>Vascular Calcification - pathology</topic><topic>Vascular Calcification - physiopathology</topic><topic>VASCULAR SMOOTH MUSCLE CELLS</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khavandgar, Zohreh</creatorcontrib><creatorcontrib>Roman, Hassem</creatorcontrib><creatorcontrib>Li, Jingjing</creatorcontrib><creatorcontrib>Lee, Sara</creatorcontrib><creatorcontrib>Vali, Hojatollah</creatorcontrib><creatorcontrib>Brinckmann, Juergen</creatorcontrib><creatorcontrib>Davis, Elaine C</creatorcontrib><creatorcontrib>Murshed, Monzur</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khavandgar, Zohreh</au><au>Roman, Hassem</au><au>Li, Jingjing</au><au>Lee, Sara</au><au>Vali, Hojatollah</au><au>Brinckmann, Juergen</au><au>Davis, Elaine C</au><au>Murshed, Monzur</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2014-02</date><risdate>2014</risdate><volume>29</volume><issue>2</issue><spage>327</spage><epage>337</epage><pages>327-337</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>ABSTRACT Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP‐deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP‐deficient (Mgp–/–) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age. The mechanism of antimineralization function of MGP is not fully understood. We examined the progression of vascular calcification and expression of several chondrogenic/osteogenic markers in the thoracic aortas of Mgp–/– mice at various ages. Although cells with chondrocyte‐like morphology have been reported in the calcified aorta, our gene expression data indicate that chondrogenic/osteogenic markers are not upregulated in the arteries prior to the initiation of calcification. Interestingly, arterial calcification in Mgp–/– mice appears first in the elastic laminae. Considering the known mineral scaffolding function of elastin (ELN), a major elastic lamina protein, we hypothesize that elastin content in the laminae is a critical determinant for arterial calcification in Mgp–/– mice. To investigate this, we performed micro–computed tomography (µCT) and histological analyses of the aortas of Mgp–/–;Eln+/– mice and show that elastin haploinsufficiency significantly reduces arterial calcification in this strain. Our data suggest that MGP deficiency leads to alterations of vascular ECM that may in turn initiate arterial calcification. © 2014 American Society for Bone and Mineral Research.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23857752</pmid><doi>10.1002/jbmr.2039</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0884-0431
ispartof Journal of bone and mineral research, 2014-02, Vol.29 (2), p.327-337
issn 0884-0431
1523-4681
language eng
recordid cdi_proquest_miscellaneous_1490900425
source MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals
subjects Aging - genetics
Aging - metabolism
Aging - pathology
Animals
Antigens, Differentiation - genetics
Antigens, Differentiation - metabolism
Aorta, Thoracic - diagnostic imaging
Aorta, Thoracic - metabolism
Aorta, Thoracic - pathology
Aorta, Thoracic - physiopathology
Durapatite - metabolism
ELASTIN
Elastin - genetics
Elastin - metabolism
KEUTEL SYNDROME
MATRIX GLA PROTEIN
Mice
Mice, Knockout
Proteins - genetics
Proteins - metabolism
VASCULAR CALCIFICATION
Vascular Calcification - diagnostic imaging
Vascular Calcification - genetics
Vascular Calcification - metabolism
Vascular Calcification - pathology
Vascular Calcification - physiopathology
VASCULAR SMOOTH MUSCLE CELLS
X-Ray Microtomography
title Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP‐Deficient Mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T20%3A44%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Elastin%20Haploinsufficiency%20Impedes%20the%20Progression%20of%20Arterial%20Calcification%20in%20MGP%E2%80%90Deficient%20Mice&rft.jtitle=Journal%20of%20bone%20and%20mineral%20research&rft.au=Khavandgar,%20Zohreh&rft.date=2014-02&rft.volume=29&rft.issue=2&rft.spage=327&rft.epage=337&rft.pages=327-337&rft.issn=0884-0431&rft.eissn=1523-4681&rft.coden=JBMREJ&rft_id=info:doi/10.1002/jbmr.2039&rft_dat=%3Cproquest_cross%3E3184307651%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1478012543&rft_id=info:pmid/23857752&rfr_iscdi=true