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Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery

Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the kn...

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Autores principales: May, Lauren T., Bartolo, Belinda A., Harrison, David G., Guzik, Tomasz, Drummond, Grant R., Figtree, Gemma A., Ritchie, Rebecca H., Rye, Kerry-Anne, de Haan, Judy B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727216/
https://www.ncbi.nlm.nih.gov/pubmed/36459456
http://dx.doi.org/10.1042/CS20210862
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author May, Lauren T.
Bartolo, Belinda A.
Harrison, David G.
Guzik, Tomasz
Drummond, Grant R.
Figtree, Gemma A.
Ritchie, Rebecca H.
Rye, Kerry-Anne
de Haan, Judy B.
author_facet May, Lauren T.
Bartolo, Belinda A.
Harrison, David G.
Guzik, Tomasz
Drummond, Grant R.
Figtree, Gemma A.
Ritchie, Rebecca H.
Rye, Kerry-Anne
de Haan, Judy B.
author_sort May, Lauren T.
collection PubMed
description Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the known and currently unknown biological mechanisms underpinning atherosclerosis, accompanied by optimization of traditional drug discovery approaches. Current animal models do not precisely recapitulate the pathobiology underpinning human CVD. Accordingly, a fundamental limitation in early-stage drug discovery has been the lack of consensus regarding an appropriate experimental in vivo model that can mimic human atherosclerosis. However, when coupled with a clear understanding of the specific advantages and limitations of the model employed, preclinical animal models remain a crucial component for evaluating pharmacological interventions. Within this perspective, we will provide an overview of the mechanisms and modalities of atherosclerotic drugs, including those in the preclinical and early clinical development stage. Additionally, we highlight recent preclinical models that have improved our understanding of atherosclerosis and associated clinical consequences and propose model adaptations to facilitate the development of new and effective treatments.
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spelling pubmed-97272162022-12-15 Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery May, Lauren T. Bartolo, Belinda A. Harrison, David G. Guzik, Tomasz Drummond, Grant R. Figtree, Gemma A. Ritchie, Rebecca H. Rye, Kerry-Anne de Haan, Judy B. Clin Sci (Lond) Cardiovascular System & Vascular Biology Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the known and currently unknown biological mechanisms underpinning atherosclerosis, accompanied by optimization of traditional drug discovery approaches. Current animal models do not precisely recapitulate the pathobiology underpinning human CVD. Accordingly, a fundamental limitation in early-stage drug discovery has been the lack of consensus regarding an appropriate experimental in vivo model that can mimic human atherosclerosis. However, when coupled with a clear understanding of the specific advantages and limitations of the model employed, preclinical animal models remain a crucial component for evaluating pharmacological interventions. Within this perspective, we will provide an overview of the mechanisms and modalities of atherosclerotic drugs, including those in the preclinical and early clinical development stage. Additionally, we highlight recent preclinical models that have improved our understanding of atherosclerosis and associated clinical consequences and propose model adaptations to facilitate the development of new and effective treatments. Portland Press Ltd. 2022-12 2022-12-02 /pmc/articles/PMC9727216/ /pubmed/36459456 http://dx.doi.org/10.1042/CS20210862 Text en © 2022 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of Monash University in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with CAUL.
spellingShingle Cardiovascular System & Vascular Biology
May, Lauren T.
Bartolo, Belinda A.
Harrison, David G.
Guzik, Tomasz
Drummond, Grant R.
Figtree, Gemma A.
Ritchie, Rebecca H.
Rye, Kerry-Anne
de Haan, Judy B.
Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title_full Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title_fullStr Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title_full_unstemmed Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title_short Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
title_sort translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery
topic Cardiovascular System & Vascular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727216/
https://www.ncbi.nlm.nih.gov/pubmed/36459456
http://dx.doi.org/10.1042/CS20210862
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