Ophélie Gourgas1, Juliana Marulanda1, Peng Zhang1, Monzur Murshed1, Marta Cerruti2. 1. From the Materials Engineering (O.G., P.Z., M.C.), Faculty of Dentistry (J.M., M.M.), Department of Medicine (M.M.), and Shriners Hospital for Children (M.M.), McGill University, Montreal, Quebec, Canada. 2. From the Materials Engineering (O.G., P.Z., M.C.), Faculty of Dentistry (J.M., M.M.), Department of Medicine (M.M.), and Shriners Hospital for Children (M.M.), McGill University, Montreal, Quebec, Canada. marta.cerruti@mcgill.ca.
Abstract
OBJECTIVE: Vascular calcification significantly increases morbidity in life-threatening diseases, and no treatments are available because of lack of understanding of the underlying molecular mechanism. Here, we study the physicochemical details of mineral nucleation and growth in an animal model that faithfully recapitulates medial arterial calcification in humans, to understand how pathological calcification is initiated on the vascular extracellular matrix. APPROACH AND RESULTS: MGP (matrix Gla protein) is a potent mineralization inhibitor. We study the evolution of medial calcification in MGP-deficient mice over the course of 5 weeks using a combination of material science techniques and find that mineral composition and crystallinity evolve over time and space. We show that calcium is adsorbed first and then amorphous calcium phosphate and octacalcium phosphate forms, which then transform into hydroxyapatite and carbonated apatite. These events are repeated after each nucleation event, providing a snapshot of the overall mineral evolution at each time point analyzed. CONCLUSIONS: Our results show that an interdisciplinary approach combining animal models and materials science can provide insights into the mechanism of vascular calcification and suggest the importance of analyzing mineral phases, rather than just overall mineralization extent, to diagnose and possibly prevent disease development.
OBJECTIVE:Vascular calcification significantly increases morbidity in life-threatening diseases, and no treatments are available because of lack of understanding of the underlying molecular mechanism. Here, we study the physicochemical details of mineral nucleation and growth in an animal model that faithfully recapitulates medial arterial calcification in humans, to understand how pathological calcification is initiated on the vascular extracellular matrix. APPROACH AND RESULTS:MGP (matrix Gla protein) is a potent mineralization inhibitor. We study the evolution of medial calcification in MGP-deficientmice over the course of 5 weeks using a combination of material science techniques and find that mineral composition and crystallinity evolve over time and space. We show that calcium is adsorbed first and then amorphous calcium phosphate and octacalcium phosphate forms, which then transform into hydroxyapatite and carbonated apatite. These events are repeated after each nucleation event, providing a snapshot of the overall mineral evolution at each time point analyzed. CONCLUSIONS: Our results show that an interdisciplinary approach combining animal models and materials science can provide insights into the mechanism of vascular calcification and suggest the importance of analyzing mineral phases, rather than just overall mineralization extent, to diagnose and possibly prevent disease development.
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2019-12-23 Impact factor: 8.311
Authors: Peter Lanzer; Fadil M Hannan; Jan D Lanzer; Jan Janzen; Paolo Raggi; Dominic Furniss; Mirjam Schuchardt; Rajesh Thakker; Pak-Wing Fok; Julio Saez-Rodriguez; Angel Millan; Yu Sato; Roberto Ferraresi; Renu Virmani; Cynthia St Hilaire Journal: J Am Coll Cardiol Date: 2021-09-14 Impact factor: 27.203