Matrix Gla protein regulates calcification of the aortic valve
Abstract Background The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP...
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| Veröffentlicht in: | The Journal of surgical research 2015-11, Vol.199 (1), p.1-6 |
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| creator | Venardos, Neil, MD Bennett, Daine, MD Weyant, Michael J., MD Reece, Thomas Brett, MD Meng, Xianzhong, MD, PhD Fullerton, David A., MD |
| description | Abstract Background The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. Materials and methods Human AVICs were isolated from normal aortic valves from explanted hearts ( n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients ( n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2–6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann–Whitney U test ( P |
| doi_str_mv | 10.1016/j.jss.2015.04.076 |
| format | Article |
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In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. Materials and methods Human AVICs were isolated from normal aortic valves from explanted hearts ( n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients ( n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2–6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann–Whitney U test ( P < 0.05). Results MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. Conclusions An important anti–calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important “anti-calcification” protein may contribute to calcification of the aortic valve.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2015.04.076</identifier><identifier>PMID: 25990696</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aortic stenosis ; Aortic Valve - metabolism ; Aortic Valve - pathology ; Aortic Valve Stenosis - metabolism ; Aortic Valve Stenosis - pathology ; Calcinosis - metabolism ; Calcinosis - pathology ; Calcium-Binding Proteins - metabolism ; Case-Control Studies ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins - metabolism ; Humans ; Immunoblotting ; Male ; Matrix Gla Protein ; Middle Aged ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; Surgery ; Valve interstitial cell</subject><ispartof>The Journal of surgical research, 2015-11, Vol.199 (1), p.1-6</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-978167ece31d17609cf1b7ce44ea70dd917cbf72df1a659631b2ab26924499e63</citedby><cites>FETCH-LOGICAL-c576t-978167ece31d17609cf1b7ce44ea70dd917cbf72df1a659631b2ab26924499e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022480415005053$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25990696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Venardos, Neil, MD</creatorcontrib><creatorcontrib>Bennett, Daine, MD</creatorcontrib><creatorcontrib>Weyant, Michael J., MD</creatorcontrib><creatorcontrib>Reece, Thomas Brett, MD</creatorcontrib><creatorcontrib>Meng, Xianzhong, MD, PhD</creatorcontrib><creatorcontrib>Fullerton, David A., MD</creatorcontrib><title>Matrix Gla protein regulates calcification of the aortic valve</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. Materials and methods Human AVICs were isolated from normal aortic valves from explanted hearts ( n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients ( n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2–6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann–Whitney U test ( P < 0.05). Results MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. Conclusions An important anti–calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important “anti-calcification” protein may contribute to calcification of the aortic valve.</description><subject>Adult</subject><subject>Aged</subject><subject>Aortic stenosis</subject><subject>Aortic Valve - metabolism</subject><subject>Aortic Valve - pathology</subject><subject>Aortic Valve Stenosis - metabolism</subject><subject>Aortic Valve Stenosis - pathology</subject><subject>Calcinosis - metabolism</subject><subject>Calcinosis - pathology</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Case-Control Studies</subject><subject>Down-Regulation</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Male</subject><subject>Matrix Gla Protein</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Surgery</subject><subject>Valve interstitial cell</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EokvhB3BBOXJJGDuOvRbSSqiCglTEAThbjjNpHbzxYjur9t_jaEsFHDhZI7_3xv4eIS8pNBSoeDM1U0oNA9o1wBuQ4hHZUFBdvRWyfUw2AIzVfAv8jDxLaYIyK9k-JWesUwqEEhuy-2xydLfVpTfVIYaMbq4iXi_eZEyVNd660VmTXZirMFb5BisTYna2Ohp_xOfkyWh8whf35zn5_uH9t4uP9dWXy08X765q20mRayW3VEi02NKBSgHKjrSXFjlHI2EYFJW2HyUbRmpEp0RLe2Z6JhTjXCkU7TnZnXIPS7_HweKco_H6EN3exDsdjNN_38zuRl-Ho-YCePl2CXh9HxDDzwVT1nuXLHpvZgxL0lQyquiWblcpPUltDClFHB_WUNArdz3pwl2v3DVwXbgXz6s_3_fg-A26CN6eBFgoHR1GnazD2eLgItqsh-D-G7_7x229m0sv_gfeYZrCEueCX1OdmAb9dS1-7Z12AB10bfsLk5Kozw</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Venardos, Neil, MD</creator><creator>Bennett, Daine, MD</creator><creator>Weyant, Michael J., MD</creator><creator>Reece, Thomas Brett, MD</creator><creator>Meng, Xianzhong, MD, PhD</creator><creator>Fullerton, David A., MD</creator><general>Elsevier 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151101</creationdate><title>Matrix Gla protein regulates calcification of the aortic valve</title><author>Venardos, Neil, MD ; Bennett, Daine, MD ; Weyant, Michael J., MD ; Reece, Thomas Brett, MD ; Meng, Xianzhong, MD, PhD ; Fullerton, David A., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-978167ece31d17609cf1b7ce44ea70dd917cbf72df1a659631b2ab26924499e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aortic stenosis</topic><topic>Aortic Valve - metabolism</topic><topic>Aortic Valve - pathology</topic><topic>Aortic Valve Stenosis - metabolism</topic><topic>Aortic Valve Stenosis - pathology</topic><topic>Calcinosis - metabolism</topic><topic>Calcinosis - pathology</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Case-Control Studies</topic><topic>Down-Regulation</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Male</topic><topic>Matrix Gla Protein</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Surgery</topic><topic>Valve interstitial cell</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Venardos, Neil, MD</creatorcontrib><creatorcontrib>Bennett, Daine, MD</creatorcontrib><creatorcontrib>Weyant, Michael J., MD</creatorcontrib><creatorcontrib>Reece, Thomas Brett, MD</creatorcontrib><creatorcontrib>Meng, Xianzhong, MD, PhD</creatorcontrib><creatorcontrib>Fullerton, David A., MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Venardos, Neil, MD</au><au>Bennett, Daine, MD</au><au>Weyant, Michael J., MD</au><au>Reece, Thomas Brett, MD</au><au>Meng, Xianzhong, MD, PhD</au><au>Fullerton, David A., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Matrix Gla protein regulates calcification of the aortic valve</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>199</volume><issue>1</issue><spage>1</spage><epage>6</epage><pages>1-6</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. Materials and methods Human AVICs were isolated from normal aortic valves from explanted hearts ( n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients ( n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2–6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann–Whitney U test ( P < 0.05). Results MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. Conclusions An important anti–calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important “anti-calcification” protein may contribute to calcification of the aortic valve.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25990696</pmid><doi>10.1016/j.jss.2015.04.076</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aortic stenosis Aortic Valve - metabolism Aortic Valve - pathology Aortic Valve Stenosis - metabolism Aortic Valve Stenosis - pathology Calcinosis - metabolism Calcinosis - pathology Calcium-Binding Proteins - metabolism Case-Control Studies Down-Regulation Enzyme-Linked Immunosorbent Assay Extracellular Matrix Proteins - metabolism Humans Immunoblotting Male Matrix Gla Protein Middle Aged Phenotype Reverse Transcriptase Polymerase Chain Reaction Surgery Valve interstitial cell |
| title | Matrix Gla protein regulates calcification of the aortic valve |
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