OX40, which belongs to the TNF-receptor family, is a costimulatory receptor that can potentiate T cell receptor signalling on the surface of T lymphocytes. The role of OX40 in non-immune systems, particularly the cardiovascular system, has not been defined. In this study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In this study, cardiac hypertrophy was induced by aortic banding in OX40 knockout (KO) mice and wild-type mice. After 8 weeks, the OX40 KO mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation as well as preserved cardiac function compared with the wild-type mice. Follow-up in vitro studies suggested that CD4+ T lymphocyte proliferation and pro-inflammatory cytokine release were significantly decreased, while anti-inflammatory cytokine release was considerably increased in OX40 KO mice compared with wild-type mice as assessed by CCK-8 assay and ELISA. Co-culturing neonatal rat cardiomyocytes with the activated supernatant of CD4+ T lymphocytes from OX40 KO mice reduced the hypertrophy response. Interestingly, OX40 KO mice with reconstituted CD4+T lymphocytes presented deteriorated cardiac remodelling. Collectively, our data indicate that OX40 regulates cardiac remodelling via the modulation of CD4+ T lymphocytes.
- cardiac remodelling
- pressure overload
- CD4+ T lymphocytes
- ©2016 The Author(s)
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