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Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications.

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.

SUBMITTER: Viegas CS

PROVIDER: S-EPMC2789615 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications.

Viegas Carla S B CS Cavaco Sofia S Neves Pedro L PL Ferreira Ana A João Alexandre A Williamson Matthew K MK Price Paul A PA Cancela M Leonor ML Simes Dina C DC

The American journal of pathology 20091105 6

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 ...[more]

PMID: 19893032

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Project description:BACKGROUND:In clinical practice, calcifications seen on computed tomographic studies within the large brain arteries are often referred to as a surrogate marker for cholesterol-mediated atherosclerosis. However, limited data exist to support the association between calcification and atherosclerosis. In this study, we examined if intracranial arterial calcifications were associated with cholesterol-mediated intracranial large artery atherosclerosis (ILAA) within the arteries of the circle of Willis in an autopsy-based sample. METHODS:We carried out a cross-sectional analysis of histopathological characteristics of brain large arteries obtained from autopsy cases. Brain large arteries were examined for evidences of calcifications, which were rated as macroscopic (coalescent) and microscopic (scattered). In addition to calcification, we also obtained measurement of the arterial wall and the presence of ILAA and nonatherosclerotic arterial fibrosis. We built hierarchical models adjusted for demographic and vascular risk factors to assess the relationship between calcification and ILAA. RESULTS:In univariate analysis, the presence of any arterial calcifications was associated with cerebral infarcts (29% vs. 14%, P<.01). Multivariate analysis revealed that among all calcifications, coalescent calcifications were not associated with ILAA. In contrast, scattered calcifications were associated with ILAA (P<.001), decreased lumen diameter (-1.87 +/- 0.41?mm, P?.001), and increased luminal stenosis (0.03% +/- 0.01%, P?.006). These findings were independent of age, sex, or other vascular risk factors. CONCLUSIONS:This study demonstrates that coalescent calcifications in brain large arteries, although associated with morbidity, are not synonymous with cholesterol-driven ILAA. Understanding the precise pathological components of cerebrovascular disease, including nonatherosclerotic arterial calcifications, will help develop individualized therapies beyond amelioration of traditional risk factors such as hyperlipidemia.

Dataset Information

Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications.

Publications

Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications.

Similar Datasets

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