OX40 regulates pressure overload-induced cardiac hypertrophy and remodelling via CD4+ T-cells

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.

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

“…In this study, we discovered that Hyp treatment was able to repress inflammatory cell infiltration into the myocardium of AB mice. Moreover, levels of inflammatory cytokines, such as IL-1a, IL-6, TNF-α, and MCP-1, which promote progression of cardiac hypertrophy and heart failure, increased in the hypertrophic hearts [26] but were normalized by Hyp treatment. We speculate that the protective effects of Hyp on cardiac dysfunction after AB surgery may be partially associated with the suppression of cardiac inflammation.…”

Aucubin protects against pressure overload‐induced cardiac remodelling via the β3‐adrenoceptor–neuronal NOS cascades

“…We traced the outlines of 40 cells for each group, as described previously (Wu et al, 2016). Cells were then incubated with the secondary antibody goat anti-mouse IRdye 800CW (926-32210; LI-COR) for 60 min.…”

“…Echocardiography was performed on anaesthetized (1.5% isoflurane) mice using a MyLab 30CV ultrasound (Biosound Esaote, Florence, Italy) with a 10 MHz linear array ultrasound transducer, as described previously (Wu et al, 2016;Xiao et al, 2017). The left ventricle (LV) was assessed in both parasternal long-axis and short-axis views at a frame rate of 120 Hz.…”

“…Haemodynamics were measured in anaesthetized (1.5% isoflurane) mice using cardiac catheterization, as described previously (Wu et al, 2016;Xiao et al, 2017). A microtip catheter transducer (SPR-839; Millar Instruments, Houston, TX, USA) was inserted into the right carotid artery and advanced into the LV.…”

“…As described previously (Wu et al, 2016;Xiao et al, 2017), hearts were excised, placed immediately in 10% potassium chloride solution to ensure that they were stopped in diastole, washed with saline solution, placed in 10% formalin and embedded in paraffin. Hearts were cut transversely close to the apex to visualize the left and right ventricles.…”