Unraveling the role of carboxylate groups and elastin particle size in medial calcification.

Autor: Song T; Department of Mining and Materials Engineering, McGill University, Montreal, Quebec H3A 0C5, Canada. Electronic address: tao.song2@mail.mcgill.ca., Cerruti M; Department of Mining and Materials Engineering, McGill University, Montreal, Quebec H3A 0C5, Canada. Electronic address: marta.cerruti@mcgill.ca.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Aug; Vol. 274 (Pt 1), pp. 133267. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1016/j.ijbiomac.2024.133267
Abstrakt: While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites are still debated. Neutral carbonyl groups and carboxylate groups are possible candidates. Also, while it is known that elastin degradation leads to calcification, it is unclear whether this is due to formation of new carboxylate groups or elastin fragmentation. In this work, we disentangle effects of carboxylate groups and particle size on elastin calcification; in doing so, we shed light on CaP mineralization sites on elastin. We find carboxylate groups accelerate calcification only in early stages; they mainly function as Ca 2+ ion chelation sites but not calcification sites. Their presence promotes formation (likely on Ca 2+ ions adsorbed on nearby carbonyl groups) of CaP minerals with high calcium-to-phosphate ratio as intermediate phases. Larger elastin particles calcify slower but reach similar amounts of CaP minerals in late stages; they promote direct formation of hydroxyapatite and CaP minerals with low calcium-to-phosphate ratio as intermediate phases. This work provides new perspectives on how carboxylate groups and elastin particle size influence calcification; these parameters can be tuned to study the mechanism of medial calcification and design drugs to inhibit the process.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: