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The disruption of invariant natural killer T cells exacerbates cardiac hypertrophy and failure caused by pressure overload in mice
| Title: | The disruption of invariant natural killer T cells exacerbates cardiac hypertrophy and failure caused by pressure overload in mice |
| Authors: | Takahashi, Masashige Browse this author | | Kinugawa, Shintaro Browse this author →KAKEN DB | | Takada, Shingo Browse this author →KAKEN DB | | Kakutani, Naoya Browse this author | | Furihata, Takaaki Browse this author →KAKEN DB | | Sobirin, Mochamad Ali Browse this author | | Fukushima, Arata Browse this author →KAKEN DB | | Obata, Yoshikuni Browse this author | | Saito, Akimichi Browse this author | | Ishimori, Naoki Browse this author →KAKEN DB | | Iwabuchi, Kazuya Browse this author →KAKEN DB | | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | cardiac failure | | cardiac hypertrophy | | hypertrophy | | inflammation | | natural killer T cells |
| Issue Date: | Mar-2020 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Experimental physiology |
| Volume: | 105 |
| Issue: | 3 |
| Start Page: | 489 |
| End Page: | 501 |
| Publisher DOI: | 10.1113/EP087652 |
| Abstract: | New Findings What is the central question of this study? We questioned whether the disruption of invariant natural killer T (iNKT) cells exacerbates left ventricular (LV) remodelling and heart failure after transverse aortic constriction in mice. What are the main findings and their importance? Pressure overload induced by transverse aortic constriction increased the infiltration of iNKT cells in mouse hearts. The disruption of iNKT cells exacerbated LV remodelling and hastened the transition from hypertrophy to heart failure, in association with the activation of mitogen-activated protein kinase signalling. Activation of iNKT cells modulated the immunological balance in this process and played a protective role against LV remodelling and failure. Chronic inflammation is involved in the development of cardiac remodelling and heart failure (HF). Invariant natural killer T (iNKT) cells, a subset of T lymphocytes, have been shown to produce various cytokines and orchestrate tissue inflammation. The pathophysiological role of iNKT cells in HF caused by pressure overload has not been studied. In the present study, we investigated whether the disruption of iNKT cells affected this process in mice. Transverse aortic constriction (TAC) and a sham operation were performed in male C57BL/6J wild-type (WT) and iNKT cell-deficient J alpha 18 knockout (KO) mice. The infiltration of iNKT cells was increased after TAC. The disruption of iNKT cells exacerbated left ventricular (LV) remodelling and hastened the transition to HF after TAC. Histological examinations also revealed that the disruption of iNKT cells induced greater myocyte hypertrophy and a greater increase in interstitial fibrosis after TAC. The expressions of interleukin-10 and tumour necrosis factor-alpha mRNA and their ratio in the LV after TAC were decreased in the KO compared with WT mice, which might indicate that the disruption of iNKT cells leads to an imbalance between T-helper type 1 and type 2 cytokines. The phosphorylation of extracellular signal-regulated kinase was significantly increased in the KO mice. The disruption of iNKT cells exacerbated the development of cardiac remodelling and HF after TAC. The activation of iNKT cells might play a protective role against HF caused by pressure overload. Targeting the activation of iNKT cells might thus be a promising candidate as a new therapeutic strategy for HF. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80499 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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