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The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification

Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that targe...

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Autores principales: Bakhshian Nik, Amirala, Ng, Hooi Hooi, Garcia Russo, Manuel, Iacoviello, Francesco, Shearing, Paul R., Bertazzo, Sergio, Hutcheson, Joshua D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225625/
https://www.ncbi.nlm.nih.gov/pubmed/35735797
http://dx.doi.org/10.3390/jcdd9060168
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author Bakhshian Nik, Amirala
Ng, Hooi Hooi
Garcia Russo, Manuel
Iacoviello, Francesco
Shearing, Paul R.
Bertazzo, Sergio
Hutcheson, Joshua D.
author_facet Bakhshian Nik, Amirala
Ng, Hooi Hooi
Garcia Russo, Manuel
Iacoviello, Francesco
Shearing, Paul R.
Bertazzo, Sergio
Hutcheson, Joshua D.
author_sort Bakhshian Nik, Amirala
collection PubMed
description Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, have elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonate treatment and timing on the disruption or promotion of vascular calcification and bone minerals in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicated that long-term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations might be associated with a higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of the bisphosphonate treatment.
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spelling pubmed-92256252022-06-24 The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification Bakhshian Nik, Amirala Ng, Hooi Hooi Garcia Russo, Manuel Iacoviello, Francesco Shearing, Paul R. Bertazzo, Sergio Hutcheson, Joshua D. J Cardiovasc Dev Dis Article Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, have elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonate treatment and timing on the disruption or promotion of vascular calcification and bone minerals in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicated that long-term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations might be associated with a higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of the bisphosphonate treatment. MDPI 2022-05-25 /pmc/articles/PMC9225625/ /pubmed/35735797 http://dx.doi.org/10.3390/jcdd9060168 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bakhshian Nik, Amirala
Ng, Hooi Hooi
Garcia Russo, Manuel
Iacoviello, Francesco
Shearing, Paul R.
Bertazzo, Sergio
Hutcheson, Joshua D.
The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title_full The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title_fullStr The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title_full_unstemmed The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title_short The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
title_sort time-dependent role of bisphosphonates on atherosclerotic plaque calcification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225625/
https://www.ncbi.nlm.nih.gov/pubmed/35735797
http://dx.doi.org/10.3390/jcdd9060168
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