Abstract
OX40, which belongs to the tumour necrosis factor (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 the present study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In the present study, cardiac hypertrophy was induced by aortic banding (AB) in OX40 knockout (KO) mice and wild-type (WT) 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 WT mice. Follow-up in vitro studies suggested that CD4+ T-lymphocyte proliferation and pro-inflammatory cytokine release were significantly decreased, whereas anti-inflammatory cytokine release was considerably increased in OX40 KO mice compared with WT mice as assessed by Cell Counting Kit-8 (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.
- Ang II
- cardiac remodelling
- CD4+ T-lymphocytes
- OX40
- pressure overload
Abbreviations
- AB,
- aortic banding;
- ACS,
- acute coronary syndrome;
- Ang II,
- angiotensin II;
- ANP,
- atrial natriuretic peptide;
- BNP,
- β-type natriuretic peptide;
- BW,
- body weight;
- CCK,
- Cell Counting Kit;
- CSA,
- cross-sectional area;
- CTGF,
- connective tissue growth factor;
- ECM,
- cardiac extracellular matrix;
- GPCR,
- G-alpha(q) protein-coupled receptor;
- HE,
- haematoxylin–eosin;
- HF,
- heart failure;
- HW,
- heart weight;
- IFN-γ,
- interferon-gamma;
- IL,
- interleukin;
- KO,
- knockout;
- LV,
- left ventricular;
- MHC,
- myosin heavy chain;
- NRCM,
- neonatal rat cardiomyocyte;
- PSR,
- Picro-Sirius red;
- ROS,
- reactive oxygen species;
- RT-PCR,
- quantitative real-time polymerase chain reaction;
- SERCA2α,
- sarcoendoplasmic reticulum Ca2+-ATPase;
- SNP,
- single nucleotide polymorphism;
- TAC,
- transverse aortic constriction;
- TL,
- tibia length;
- TNF,
- tumour necrosis factor;
- WGA,
- wheat germ agglutinin;
- WT,
- wild-type
- © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society