دورية أكاديمية
Fibroblast-specific deletion of interleukin-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction.
| العنوان: | Fibroblast-specific deletion of interleukin-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction. |
|---|---|
| المؤلفون: | 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. |
| المصدر: | JCI insight [JCI Insight] 2019 Aug 08; Vol. 5. Date of Electronic Publication: 2019 Aug 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Fibroblasts/*metabolism , Myocardial Infarction/*metabolism , Receptors, Interleukin-1 Type I/*metabolism , Ventricular Remodeling/*physiology, Animals ; Cytokines/metabolism ; Disease Models, Animal ; Fibrosis/metabolism ; Heart Failure ; Interleukin-1alpha/genetics ; Interleukin-1alpha/metabolism ; Male ; Mice ; Mice, Knockout ; Myocardial Infarction/pathology ; Myocardium/metabolism ; Myocardium/pathology ; Myocytes, Cardiac/metabolism ; Receptors, Interleukin-1 Type I/genetics ; Signal Transduction |
| مستخلص: | 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. |
| References: | Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H176-83. (PMID: 16473963) PLoS One. 2011;6(11):e27923. (PMID: 22140485) Am J Physiol. 1995 Aug;269(2 Pt 2):R229-35. (PMID: 7544543) Sci Signal. 2010 Jan 19;3(105):cm1. (PMID: 20086235) Circ Heart Fail. 2018 Aug;11(8):e005036. (PMID: 30354558) Eur J Immunol. 2016 Apr;46(4):912-8. (PMID: 26692072) Am J Cardiol. 2013 May 15;111(10):1394-400. (PMID: 23453459) J Am Coll Cardiol. 2017 Oct 31;70(18):2278-2289. (PMID: 29073957) J Invest Dermatol. 2009 Jan;129(1):194-204. (PMID: 18563179) J Immunol. 2013 Nov 1;191(9):4838-48. (PMID: 24078695) Nature. 2014 Oct 30;514(7524):585-90. (PMID: 25317562) Circ Res. 2016 Feb 5;118(3):400-9. (PMID: 26635390) J Mol Cell Cardiol. 2015 Sep;86:54-61. (PMID: 26141530) J Histochem Cytochem. 2013 Aug;61(8):555-70. (PMID: 23714783) Dis Model Mech. 2015 Aug 1;8(8):783-94. (PMID: 26092119) J Cardiovasc Pharmacol. 2017 Mar;69(3):156-160. (PMID: 28267688) Circulation. 2014 Jul 29;130(5):419-30. (PMID: 24899689) Am J Pathol. 2008 Jul;173(1):57-67. (PMID: 18535174) Biochim Biophys Acta. 2013 Apr;1833(4):945-53. (PMID: 22982064) Am J Cardiol. 2010 May 15;105(10):1371-1377.e1. (PMID: 20451681) Cell Death Differ. 2016 Jul;23(7):1219-31. (PMID: 26868913) Discoveries (Craiova). 2015 Jan-Mar;3(1):. (PMID: 26273700) J Immunol. 2015 Jan 15;194(2):499-503. (PMID: 25505286) PLoS One. 2010 Jun 22;5(6):e11260. (PMID: 20582321) JACC Basic Transl Sci. 2017 Aug 28;2(4):418-430. (PMID: 30062160) FASEB J. 2018 Sep;32(9):4941-4954. (PMID: 29601781) Vascul Pharmacol. 2014 Jan;60(1):1-7. (PMID: 23806284) Nature. 2011 Jun 15;474(7351):337-42. (PMID: 21677750) Eur Heart J. 2015 Feb 7;36(6):377-84. (PMID: 25079365) Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2051-8. (PMID: 25012136) Hypertension. 2016 Oct;68(4):937-48. (PMID: 27550917) Cell Signal. 2001 Apr;13(4):269-77. (PMID: 11306244) Br J Pharmacol. 2018 May;175(9):1377-1400. (PMID: 29394499) Eur Heart J. 2018 Jun 7;39(22):2063-2069. (PMID: 29584915) N Engl J Med. 2017 Sep 21;377(12):1119-1131. (PMID: 28845751) Am J Pathol. 2002 May;160(5):1609-17. (PMID: 12000713) Nat Med. 2007 Jul;13(7):851-6. (PMID: 17572686) J Endocrinol. 2017 Jun;233(3):315-327. (PMID: 28522730) World J Cardiol. 2016 May 26;8(5):340-50. (PMID: 27231521) Exp Physiol. 2013 Mar;98(3):734-45. (PMID: 23180808) J Mol Cell Cardiol. 2016 May;94:189-200. (PMID: 26542796) |
| معلومات مُعتمدة: | PG/11/80/29135 United Kingdom BHF_ British Heart Foundation; PG/13/55/30365 United Kingdom BHF_ British Heart Foundation; PG/16/31/32130 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: Cardiology; Cytokines; Fibrosis; Heart failure; Inflammation |
| المشرفين على المادة: | 0 (Cytokines) 0 (IL1R1 protein, mouse) 0 (Il1a protein, mouse) 0 (Interleukin-1alpha) 0 (Receptors, Interleukin-1 Type I) |
| تواريخ الأحداث: | Date Created: 20190809 Date Completed: 20200914 Latest Revision: 20240720 |
| رمز التحديث: | 20240720 |
| مُعرف محوري في PubMed: | PMC6777910 |
| DOI: | 10.1172/jci.insight.125074 |
| PMID: | 31393855 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
|---|---|
| DOI: | 10.1172/jci.insight.125074 |