Fibroblast-specific deletion of interleukin-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction.

Autor:	Bageghni SA; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Hemmings KE; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Yuldasheva NY; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Maqbool A; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Gamboa-Esteves FO; Leeds Institute of Cancer and Pathology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom., Humphreys NE; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Jackson MS; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Denton CP; Institute of Immunity and Transplantation, Centre for Rheumatology and Connective Tissue Diseases, University College London and Royal Free Hospital, London, United Kingdom., Francis S; Department of Infection, Immunity & Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, United Kingdom., Porter KE; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Ainscough JF; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Pinteaux E; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Drinkhill MJ; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom., Turner NA; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2019 Aug 08; Vol. 5. Date of Electronic Publication: 2019 Aug 08.
DOI:	10.1172/jci.insight.125074
Abstrakt:	It has been hypothesized that interleukin-1alpha (IL-1α) is released from damaged cardiomyocytes following myocardial infarction (MI) and activates cardiac fibroblasts via its receptor (IL-1R1) to drive the early stages of cardiac remodeling. This study aimed to definitively test this hypothesis using cell type-specific IL-1α and IL-1R1 knockout (KO) mouse models. A floxed Il1α mouse was created and used to generate a cardiomyocyte-specific IL-1α KO mouse line (MIL1AKO). A tamoxifen-inducible fibroblast-specific IL-1R1 hemizygous KO mouse line (FIL1R1KO) was also generated. Mice underwent experimental MI (permanent left anterior descending coronary artery ligation) and cardiac function was determined 4 weeks later by conductance pressure-volume catheter analysis. Molecular markers of remodeling were evaluated at various time points by real-time RT-PCR and histology. MIL1AKO mice showed no difference in cardiac function or molecular markers of remodeling post-MI compared with littermate controls. In contrast, FIL1R1KO mice showed improved cardiac function and reduced remodeling markers post-MI compared with littermate controls. In conclusion, these data highlight a key role for the IL-1R1/cardiac fibroblast signaling axis in regulating post-MI remodeling and provide support for the continued development of anti-IL-1 therapies for improving cardiac function after MI. Cardiomyocyte-derived IL-1α was not an important contributor to post-MI remodeling in this model.
Databáze:	MEDLINE
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