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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
04 03 2021
Historique:
received: 15 01 2021
accepted: 22 02 2021
entrez: 5 3 2021
pubmed: 6 3 2021
medline: 15 12 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33664407
doi: 10.1038/s41598-021-84812-7
pii: 10.1038/s41598-021-84812-7
pmc: PMC7933438
doi:

Substances chimiques

Angiotensin-Converting Enzyme Inhibitors 0
Captopril 9G64RSX1XD

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5241

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Auteurs

Urmas Roostalu (U)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark. uro@gubra.dk.

Louise Thisted (L)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Jacob Lercke Skytte (JL)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Casper Gravesen Salinas (CG)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Philip Juhl Pedersen (PJ)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Jacob Hecksher-Sørensen (J)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Bidda Rolin (B)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.
Novo Nordisk, 2760, Maaloev, Denmark.

Henrik H Hansen (HH)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

James G MacKrell (JG)

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.

Robert M Christie (RM)

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.

Niels Vrang (N)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Jacob Jelsing (J)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

Nora Elisabeth Zois (NE)

Gubra, Hørsholm Kongevej 11, B, 2970, Hørsholm, Denmark.

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