| 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 |
| Contributors: |
British Heart Foundation; Leducq Foundation for Cardiovascular Research; Wellcome Trust |
| Source: |
243 ; 229 |
| Publisher Information: |
Wiley |
| Publication Year: |
2020 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
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; REGENERATION; EXPRESSION; auto-antibodies; 0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and Cell Biology; 1103 Clinical Sciences; Biochemistry & Molecular Biology |
| Subject Geographic: |
England |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Journal of Cellular and Molecular Medicine; http://hdl.handle.net/10044/1/84466; 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 |
| DOI: |
10.1111/jcmm.15937 |
| Availability: |
http://hdl.handle.net/10044/1/84466; https://doi.org/10.1111/jcmm.15937 |
| Rights: |
© 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. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.1EB2308F |
| Database: |
BASE |