| First Author | Bageghni SA | Year | 2019 |
| Journal | JCI Insight | Volume | 5 |
| PubMed ID | 31393855 | Mgi Jnum | J:280743 |
| Mgi Id | MGI:6369529 | Doi | 10.1172/jci.insight.125074 |
| Citation | Bageghni SA, et al. (2019) Fibroblast-specific deletion of interleukin-1 receptor-1 reduces adverse cardiac remodeling following myocardial infarction. JCI Insight 5 |
| abstractText | It has been hypothesized that interleukin-1alpha (IL-1alpha) 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-1alpha and IL-1R1 knockout (KO) mouse models. A floxed Il1alpha mouse was created and used to generate a cardiomyocyte-specific IL-1alpha 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-1alpha was not an important contributor to post-MI remodeling in this model. |
