Interruption of the Tnfrsf4/Tnfsf4 (OX40/OX40L) pathway attenuates atherogenesis in low-density lipoprotein receptor-deficient mice
EJA van Wanrooij, GHM van Puijvelde… - … , and vascular biology, 2007 - Am Heart Assoc
EJA van Wanrooij, GHM van Puijvelde, P de Vos, H Yagita, TJC van Berkel, J Kuiper
Arteriosclerosis, thrombosis, and vascular biology, 2007•Am Heart AssocObjective—Atherosclerosis is a chronic (auto-) inflammatory disease and T cell activation is
an important factor in this process. Tnfrsf4 (OX40) and Tnfsf4 (OX40 ligand) are members of
the tumor necrosis factor (TNF) and TNF receptor family and OX40/OX40L mediated
signaling is important in co-activation of T cells and facilitates BT cell interaction. In this study
we assessed the role of the OX40/OX40L pathway in atherosclerosis and the effect of
interruption of the OX40/OX40L pathway on lesion development. Methods and Results—We …
an important factor in this process. Tnfrsf4 (OX40) and Tnfsf4 (OX40 ligand) are members of
the tumor necrosis factor (TNF) and TNF receptor family and OX40/OX40L mediated
signaling is important in co-activation of T cells and facilitates BT cell interaction. In this study
we assessed the role of the OX40/OX40L pathway in atherosclerosis and the effect of
interruption of the OX40/OX40L pathway on lesion development. Methods and Results—We …
Objective— Atherosclerosis is a chronic (auto-)inflammatory disease and T cell activation is an important factor in this process. Tnfrsf4 (OX40) and Tnfsf4 (OX40 ligand) are members of the tumor necrosis factor (TNF) and TNF receptor family and OX40/OX40L mediated signaling is important in co-activation of T cells and facilitates B-T cell interaction. In this study we assessed the role of the OX40/OX40L pathway in atherosclerosis and the effect of interruption of the OX40/OX40L pathway on lesion development.
Methods and Results— We treated low-density lipoprotein receptor-deficient (LDLr−/−) mice with an anti-OX40L antibody which lead to a 53% decrease in atherosclerotic lesion formation. Treatment resulted in inhibition of Th2 mediated isotype switching by decreasing interleukin (IL)-4 secretion and subsequent low IgG1 serum levels against oxLDL, whereas protective anti-oxLDL specific IgM titers were increased in treated mice compared with control.
Conclusions— We conclude that blocking the OX-40/OX40L interaction reduced atherogenesis by inhibition of IL-4 mediated Th2 induced isotype switching and subsequent increased levels of anti-oxLDL IgM.
Am Heart Assoc
