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Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart

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Title: Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart
Authors: Forte, E
Panahi, M
Baxan, N
Ng, FS
Boyle, JJ
Branca, J
Bedard, O
Hasham, MG
Benson, L
Harding, SE
Rosenthal, N
Sattler, S
Item Type: Journal Article
Abstract: Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß-adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis. To assess whether isoproterenol-induced cardiomyocyte necrosis triggers an adaptive immune response against the heart, we treated C57BL/6J mice with a single intraperitoneal injection of isoproterenol. We confirmed tissue damage reminiscent of human type 2 myocardial infarction. This is followed by an adaptive immune response targeting the heart as demonstrated by the activation of T cells, the presence of anti-heart auto-antibodies in the serum as late as 12 weeks after initial challenge and IgG deposition in the myocardium. All of these are hallmark signs of an established autoimmune response. Adoptive transfer of splenocytes from isoproterenol-treated mice induces left ventricular dilation and impairs cardiac function in healthy recipients. In summary, a single administration of a high dose of isoproterenol is a suitable high-throughput model for future studies of the pathological mechanisms of anti-heart autoimmunity and to test potential immunomodulatory therapeutic approaches.
Issue Date: Jan-2021
Date of Acceptance: 6-Sep-2020
URI: http://hdl.handle.net/10044/1/84466
DOI: 10.1111/jcmm.15937
ISSN: 1582-1838
Publisher: Wiley
Start Page: 229
End Page: 243
Journal / Book Title: Journal of Cellular and Molecular Medicine
Volume: 25
Issue: 1
Copyright Statement: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Leducq Foundation for Cardiovascular Research
Wellcome Trust
British Heart Foundation
Funder's Grant Number: RM/17/1/33377
FS/13/12/30037
SCRF03
PG/17/71/33242
RG/16/3/32175
13 CVD 01
105603/Z/14/Z
PG/16/93/32345
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
adaptive immune system
auto‐
antibodies
autoimmunity
fibrosis
inflammation
isoprenaline
isoproterenol
myocardial infarction
type 2 myocardial infarction
INDUCED MYOCARDIAL NECROSIS
MOUSE MODEL
INFARCTION
FAILURE
INJURY
CELLS
CATECHOLAMINES
AUTOIMMUNITY
REGENERATION
EXPRESSION
adaptive immune system
auto-antibodies
autoimmunity
fibrosis
inflammation
isoprenaline
isoproterenol
myocardial infarction
type 2 myocardial infarction
adaptive immune system
auto-antibodies
autoimmunity
fibrosis
inflammation
isoprenaline
isoproterenol
myocardial infarction
type 2 myocardial infarction
0304 Medicinal and Biomolecular Chemistry
0601 Biochemistry and Cell Biology
1103 Clinical Sciences
Biochemistry & Molecular Biology
Publication Status: Published
Conference Place: England
Open Access location: https://pubmed.ncbi.nlm.nih.gov/33249764/
Online Publication Date: 2020-11-29
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons