Author + information
- Li Bo,
- JiaYi Weng,
- CuiPing Wang,
- Zhongqun Wang,
- Wei Zhong and
- Jinchuan Yan
Angiogenesis is a key feature of vulnerable atherosclerotic plaques prone to rupture, and is the consequence of inappropriate angiogenic signaling. The costimulatory molecules of the tumor necrosis factor receptor (TNFR) superfamily such as CD40/CD40L were shown to be pluripotent in both angiogenesis and atheroscletotic development. CD137, the immunologic mediator of the TNF superfamily members is expressed in human atherosclerotic lesions, by endothelial. Here, we aim to investigate the role and the mechanism of CD137 in atherosclerostic angiogenesis.
In vivo, Apolipoprotein E-deficient (ApoE-/) mouse was used as model. Masson and Immunohistochemical analysis of atherosclerotic plaques and matrigel plug assay were assessed. In ex vivo and vivo, human umbilical vein endothelial cells (HUVEC) and mouse brain endothelial cells were used as models. Matrigel tube formation assay, mouse aortic ring angiogenesis assay and migration and proliferation assay were assessed. Western blot was used to detect protein expression.
In vivo, we found that activating CD137 signaling induced neovessel formation in ApoE-/mouse atherosclerotic plaques. In ex vivo and in vitro, we demonstrated that the supplementation with agonist-CD137 antibody could induce angiogenesis, endothelial proliferation and endothelial migration. CD137 activates the pro-angiogenic Smad1/5 pathway, induces the phosphorylation of Smad1/5 and promotes nuclear translocation of P-Smad1/5, which results in the expression and translocation of NFATc1. Meanwhile, anti-CD137 antibody could inhibit this activation and attenuated CD137- induced angiogenesis.
CD137 is a new regulator of angiogenesis and mediates by modulating Smad1/5-NFATc1 signaling.