Journal Article
Title | Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications. |
Publication Type | Journal Article |
Authors | Viegas, CSB, Cavaco, S, Neves, PL, Ferreira, A, João, A, Williamson, MK, Price, PA, M. Cancela, L, Simes, DC |
Year of Publication | 2009 |
Journal | Am J Pathol |
Volume | 175 |
Issue | 6 |
Date Published | 2009 Dec |
Pagination | 2288-98 |
ISSN | 1525-2191 |
Keywords | Animals, Blood Vessels, Blotting, Western, Calcinosis, Electrophoresis, Polyacrylamide Gel, Gene Expression, Humans, In Situ Hybridization, Osteocalcin, Rats, Reverse Transcriptase Polymerase Chain Reaction, Skin, Swine |
Abstract | Mineralization 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. |
DOI | 10.2353/ajpath.2009.090474 |
Sapientia | |
Alternate Journal | Am. J. Pathol. |
PubMed ID | 19893032 |
PubMed Central ID | PMC2789615 |
Grant List | R01 HL058090 / HL / NHLBI NIH HHS / United States HL58090 / HL / NHLBI NIH HHS / United States |