Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography

Abstract Angiotensin converting enzyme inhibitors, among them captopril, improve survival following myocardial infarction (MI). The mechanisms of captopril action remain inadequately understood due to its diverse effects on multiple signalling pathways at different time periods following MI. Here we...

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Autores principales:	Urmas Roostalu, Louise Thisted, Jacob Lercke Skytte, Casper Gravesen Salinas, Philip Juhl Pedersen, Jacob Hecksher-Sørensen, Bidda Rolin, Henrik H. Hansen, James G. MacKrell, Robert M. Christie, Niels Vrang, Jacob Jelsing, Nora Elisabeth Zois
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5eb67c5b398c476eaf57ac9ff978429a
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spelling	oai:doaj.org-article:5eb67c5b398c476eaf57ac9ff978429a2021-12-02T13:30:10ZEffect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography10.1038/s41598-021-84812-72045-2322https://doaj.org/article/5eb67c5b398c476eaf57ac9ff978429a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84812-7https://doaj.org/toc/2045-2322Abstract Angiotensin converting enzyme inhibitors, among them captopril, improve survival following myocardial infarction (MI). The mechanisms of captopril action remain inadequately understood due to its diverse effects on multiple signalling pathways at different time periods following MI. Here we aimed to establish the role of captopril in late-stage post-MI remodelling. Left anterior descending artery (LAD) ligation or sham surgery was carried out in male C57BL/6J mice. Seven days post-surgery LAD ligated mice were allocated to daily vehicle or captopril treatment continued over four weeks. To provide comprehensive characterization of the changes in mouse heart following MI a 3D light sheet imaging method was established together with automated image analysis workflow. The combination of echocardiography and light sheet imaging enabled to assess cardiac function and the underlying morphological changes. We show that delayed captopril treatment does not affect infarct size but prevents left ventricle dilation and hypertrophy, resulting in improved ejection fraction. Quantification of lectin perfused blood vessels showed improved vascular density in the infarct border zone in captopril treated mice in comparison to vehicle dosed control mice. These results validate the applicability of combined echocardiographic and light sheet assessment of drug mode of action in preclinical cardiovascular research.Urmas RoostaluLouise ThistedJacob Lercke SkytteCasper Gravesen SalinasPhilip Juhl PedersenJacob Hecksher-SørensenBidda RolinHenrik H. HansenJames G. MacKrellRobert M. ChristieNiels VrangJacob JelsingNora Elisabeth ZoisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Urmas Roostalu Louise Thisted Jacob Lercke Skytte Casper Gravesen Salinas Philip Juhl Pedersen Jacob Hecksher-Sørensen Bidda Rolin Henrik H. Hansen James G. MacKrell Robert M. Christie Niels Vrang Jacob Jelsing Nora Elisabeth Zois Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
description	Abstract Angiotensin converting enzyme inhibitors, among them captopril, improve survival following myocardial infarction (MI). The mechanisms of captopril action remain inadequately understood due to its diverse effects on multiple signalling pathways at different time periods following MI. Here we aimed to establish the role of captopril in late-stage post-MI remodelling. Left anterior descending artery (LAD) ligation or sham surgery was carried out in male C57BL/6J mice. Seven days post-surgery LAD ligated mice were allocated to daily vehicle or captopril treatment continued over four weeks. To provide comprehensive characterization of the changes in mouse heart following MI a 3D light sheet imaging method was established together with automated image analysis workflow. The combination of echocardiography and light sheet imaging enabled to assess cardiac function and the underlying morphological changes. We show that delayed captopril treatment does not affect infarct size but prevents left ventricle dilation and hypertrophy, resulting in improved ejection fraction. Quantification of lectin perfused blood vessels showed improved vascular density in the infarct border zone in captopril treated mice in comparison to vehicle dosed control mice. These results validate the applicability of combined echocardiographic and light sheet assessment of drug mode of action in preclinical cardiovascular research.
format	article
author	Urmas Roostalu Louise Thisted Jacob Lercke Skytte Casper Gravesen Salinas Philip Juhl Pedersen Jacob Hecksher-Sørensen Bidda Rolin Henrik H. Hansen James G. MacKrell Robert M. Christie Niels Vrang Jacob Jelsing Nora Elisabeth Zois
author_facet	Urmas Roostalu Louise Thisted Jacob Lercke Skytte Casper Gravesen Salinas Philip Juhl Pedersen Jacob Hecksher-Sørensen Bidda Rolin Henrik H. Hansen James G. MacKrell Robert M. Christie Niels Vrang Jacob Jelsing Nora Elisabeth Zois
author_sort	Urmas Roostalu
title	Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
title_short	Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
title_full	Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
title_fullStr	Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
title_full_unstemmed	Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
title_sort	effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5eb67c5b398c476eaf57ac9ff978429a
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Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography

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