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Gla-Rich Protein Is a Novel Vitamin K-Dependent Protein Present in Serum That Accumulates at Sites of Pathological Calcifications

2009-12Journal article Open Access
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dc.contributor.authorViegas, Carla
dc.contributor.authorCavaco, Sofia
dc.contributor.authorNeves, Pedro L.
dc.contributor.authorFerreira, Ana
dc.contributor.authorJoao, Alexandre
dc.contributor.authorWilliamson, Matthew K.
dc.contributor.authorPrice, Paul A.
dc.contributor.authorCancela, M. Leonor
dc.contributor.authorSimes, Dina
dc.date.accessioned2018-12-07T14:52:50Z
dc.date.available2018-12-07T14:52:50Z
dc.date.issued2009-12
dc.description.abstractMineralization of soft tissues is an abnormal process that occurs in any body tissue and can greatly increase morbidity and mortality. Vitamin K-dependent (VKD) proteins play a crucial role in these processes; matrix Gla protein is considered one of the most relevant physiological inhibitors of soft tissue calcification know to date. Several studies have suggested that other, still unknown, VKD proteins might also be involved in soft tissue calcification pathologies. We have recently identified in sturgeon a new VKD protein, Gla-rich protein (GRP), which contains the highest ratio between number of Gla residues and size of the mature protein so far identified. Although mainly expressed in cartilaginous tissues of sturgeon, in rat GRP is present in both cartilage and bone. We now show that GRP is a circulating protein that is also expressed and accumulated in soft tissues of rats and humans, including the skin and vascular system in which, when affected by pathological calcifications, GRP accumulates at high levels at sites of mineral deposition, indicating an association with calcification processes. The high number of Gla residues and consequent mineral binding affinity properties strongly suggest that GRP may directly influence mineral formation, thereby playing a role in processes involving connective tissue mineralization. (Am J Pathol 2009, 175:2288-2298; DOI; 10.2353/ajpath.2009.090474)
dc.description.sponsorshipNHLBI NIH HHS [HL58090, R01 HL058090]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.2353/ajpath.2009.090474
dc.identifier.issn0002-9440
dc.identifier.urihttp://hdl.handle.net/10400.1/11232
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmer Soc Investigative Pathology, Inc
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGamma-carboxyglutamic acid
dc.subjectLow-dose Warfarin
dc.subjectPseudoxanthoma-elasticum
dc.subjectKeutel-syndrome
dc.subjectCalcinosis universalis
dc.subjectVascular calcification
dc.subjectArterial calcification
dc.subjectEctopic calcification
dc.subjectCutis Laxa
dc.subjectCartilage
dc.titleGla-Rich Protein Is a Novel Vitamin K-Dependent Protein Present in Serum That Accumulates at Sites of Pathological Calcifications
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2298
oaire.citation.issue6
oaire.citation.startPage2288
oaire.citation.titleAmerican Journal of Pathology
oaire.citation.volume175
person.familyNameViegas
person.familyNameCavaco
person.familyNameCancela
person.familyNameSimes
person.givenNameCarla
person.givenNameSofia
person.givenNameM. Leonor
person.givenNameDina
person.identifier.ciencia-idC414-F596-EEC6
person.identifier.ciencia-id9317-E1FC-06F0
person.identifier.orcid0000-0002-5765-3665
person.identifier.orcid0000-0001-7315-4543
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-5145-4753
person.identifier.ridN-6695-2014
person.identifier.ridN-2789-2014
person.identifier.scopus-author-id8656310300
person.identifier.scopus-author-id6506957933
person.identifier.scopus-author-id7201884723
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication33984b3c-ffac-477a-896a-ddbf7aced4e3
relation.isAuthorOfPublication643e5c34-4f43-41b7-b7c6-274639742128
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication31bac96d-1d01-4b8f-8f2b-9da4be31ea41
relation.isAuthorOfPublication.latestForDiscoveryb9bbfe32-3dfe-4131-ad14-a4394008447f

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