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...
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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. |
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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 & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>ProQuest Health & 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> |
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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 |
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