| First Author | Enomoto D | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0183584 |
| PubMed ID | 28827845 | Mgi Jnum | J:247135 |
| Mgi Id | MGI:5918579 | Doi | 10.1371/journal.pone.0183584 |
| Citation | Enomoto D, et al. (2017) RORgammat-expressing cells attenuate cardiac remodeling after myocardial infarction. PLoS One 12(8):e0183584 |
| abstractText | AIMS: Retinoic acid receptor-related orphan nuclear receptor gammat (RORgammat) is a transcriptional factor responsible for IL-17-producing T-cell differentiation. Although it was demonstrated that RORgammat plays essential roles in the onset of autoimmune myocarditis, pathophysiological significance of RORgammat in cardiac remodeling after myocardial infarction (MI) remains to be fully elucidated. METHODS AND RESULTS: MI was generated by ligating coronary artery. The expression of RORgammat and IL-17A transcripts increased in murine hearts after MI. Additionally, immunohistochemical staining revealed that RORgammat-expressing cells infiltrated in the border zone after MI. Flow cytometric analysis showed that RORgammat-expressing cells were released from the spleen at day 1 after MI. Though RORgammat-expressing cells in spleen expressed gammadeltaTCR or CD4, gammadeltaTCR+ cells were major population of RORgammat-expressing cells that infiltrated into post-infarct myocardium. To address the biological functions of RORgammat-expressing cells in infarcted hearts, we used mice with enhanced GFP gene heterozygously knocked-in at RORgammat locus (RORgammat+/- mice), which physiologically showed reduced expression of RORgammat mRNA in thymus. Kaplan-Meier analysis showed that MI-induced mortality was higher in RORgammat+/- mice than wild-type (WT) mice. Masson's trichrome staining demonstrated that cardiac injury was exacerbated in RORgammat+/- mice 7 days after MI (Injured area: RORgammat+/-; 42.1+/-6.5%, WT; 34.0+/-3.7%, circumference of injured myocardium: RORgammat+/-; 61.8+/-4.8%, WT; 49.6+/-5.1%), accompanied by exacerbation of cardiac function (fractional shortening: RORgammat+/-; 32.9+/-2.9%, WT; 38.3+/-3.6%). Moreover, immunohistochemical analyses revealed that capillary density in border zone was significantly reduced in RORgammat+/- mice after MI, compared with WT mice, associated with the reduced expression of angiopoietin 2. Finally, the mRNA expression of RORgammat, IL-17A, IL-17F and IL-23 receptor (IL-23R) mRNA and protein expression of IL-10 were decreased in RORgammat+/- hearts. CONCLUSIONS: Heterozygous deletion of RORgammat gene resulted in aggravated cardiac remodeling, accompanied by reduced capillary density, after MI, suggesting that RORgammat-expressing cells contribute to tissue repair in infarcted myocardium. |
