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Investigation of cardiac fibroblasts using myocardial slices

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Title: Investigation of cardiac fibroblasts using myocardial slices
Authors: Perbellini, F
Watson, SA
Scigliano, M
Alayoubi, S
Tkach, S
Bardi, I
Quaife, N
Kane, C
Dufton, NP
Simon, A
Sikkel, MB
Faggian, G
Randi, AM
Gorelik, J
Harding, S
Terracciano, CMN
Item Type: Journal Article
Abstract: Aims Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices. Methods and results Unloading of myocardial slices induced CF proliferation without α-SMA expression up to 7 days in culture. CFs migrating onto the culture plastic support or cultured on glass expressed αSMA within 3 days. The cells on the slice remained αSMA(−) despite transforming growth factor-β (20 ng/ml) or angiotensin II (200 µM) stimulation. When diastolic load was applied to myocardial slices using A-shaped stretchers, CF proliferation was significantly prevented at Days 3 and 7 (P < 0.001). Conclusions Myocardial slices allow the study of CFs in a multicellular environment and may be used to effectively study mechanisms of cardiac fibrosis and potential targets.
Issue Date: 18-Aug-2017
Date of Acceptance: 4-Aug-2017
URI: http://hdl.handle.net/10044/1/50360
DOI: https://dx.doi.org/10.1093/cvr/cvx152
ISSN: 1755-3245
Publisher: Elsevier
Start Page: 77
End Page: 89
Journal / Book Title: Cardiovascular Research
Volume: 114
Issue: 1
Copyright Statement: © The Author 2017. Published on behalf of the European Society of Cardiology This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: British Heart Foundation
Funder's Grant Number: RM/13/1/30157
Keywords: Cardiac fibroblasts
Mechanical load
Myocardial slices
1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute