Gla-Rich Protein Acts as a Calcification Inhibitor in the Human Cardiovascular System

• DOI: 10.1161/atvbaha.114.304823
• Publication Date: 2014-12-24T05:19:40Z
• Authors: Carla S.B. Viegas; Marta S. Rafael; José L. Enriquez; Alexandra Teixeira; Rui Vitorino; Inês M. Luís; Rúben M. Costa; Sofia Santos; Sofia Cavaco; José Neves; Anjos L. Macedo; Brecht A.G. Willems; Cees Vermeer; Dina C. Simes
• Keywords: Adult; Male; 0301 basic medicine; Coronary Artery Disease; 03 medical and health sciences; Humans; Aorta; Aged; Aged, 80 and over; Extracellular Matrix Proteins; calcification of; Calcium-Binding Proteins; Intracellular Signaling Peptides and Proteins; Calcinosis; Aortic Valve Stenosis; aortic valve; multivesicular bodies; Coronary Vessels; Actins; 3. Good health; Gene Expression Regulation; vascular calcification; Aortic Valve; Case-Control Studies; gene expression; Intercellular Signaling Peptides and Proteins; Calcium; Female

Vascular and valvular calcifications are pathological processes regulated by resident cells, depending on a complex interplay between calcification promoters inhibitors, resembling skeletal metabolism. Here, we study the role of vitamin K-dependent Gla-rich protein (GRP) in vascular processes.Immunohistochemistry quantitative polymerase chain reaction showed that GRP expression accumulation upregulated with simultaneously osteocalcin matrix Gla (MGP). Using conformation-specific antibodies, both γ-carboxylated undercarboxylated species were found accumulated at sites mineral deposits, whereas was predominant calcified aortic valve disease interstitial cells. Mineral-bound GRP, MGP, fetuin-A identified mass spectrometry. an ex vivo model calcification, but not shown to inhibit osteochondrogenic differentiation through α-smooth muscle actin upregulation osteopontin downregulation. Immunoprecipitation assays is part MGP-fetuin-A calcification. Moreover, extracellular vesicles released from normal smooth cells loaded fetuin-A, under calcifying conditions, show increased calcium loading MGP depletion.GRP inhibitor involved homeostasis. Its function might be associated prevention calcium-induced signaling pathways direct binding crystal formation/maturation. Our data new player mineralization competence possibly fetuin-A-MGP inhibitory system. activity dependent its γ-carboxylation status, potential clinical relevance.