Author + information
- Li Bo,
- Yao Chen,
- Juan Song,
- Zhongqun Wang,
- Wei Zhong and
- Jinchuan Yan
Vascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular morbidity and mortality. CD137 signaling, CD137-CD137L interaction, has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In this study, we aim to investigated the effect of CD137 signaling in vascular calcification in vivo and vitro.
Vascular smooth muscle cells (VSMCs) were isolated from C57BL/6J. ApoE-/- mice (8 weeks) received a high fat diet for 4 weeks, after which the mice were randomly divided into the following groups: agonist-CD137 group, anti-CD137 group, and control group. Mice in each group were intraperitoneally injected with 200 μg agonist-CD137 antibody, 200μg anti-CD137 antibody + 200μg agonist-CD137 antibody, or 200μg IgG 2b at 13, 15, and 17 weeks of age respectively.
Agonist-CD137 demonstrated increased areas of vascular calcification, as well as increased bone morphogenic proteins 2 (BMP2), runt-related transcription factor 2 (Runx2) expression. In vitro, activation of CD137 signaling with agonist-CD137 aggravated VSMCs calcification, while blocking CD137 signaling with additionally anti-CD137 alleviated agonist-CD137 induced VSMCs calcification. Consistent with this, the levels of calcium, BMP2 and Runx2 were significant elevated in agonist-CD137 group.
Activation of CD137 accelerates vascular calcification in vivo and vitro, and that CD137 signaling plays an important role in differentiation of VSMCs to osteogenic cells.