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Title 

CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs

Authors 

W LiM FebbraioS P ReddyDae Yeul YuM YamamotoR L Silverstein

Publisher 

American Society for Clinical Investigation

Issue Date 

2010

Citation 

Journal of Clinical Investigation, vol. 120, no. 11, pp. 3996-4006

Abstract 

CD36 is a membrane glycoprotein expressed on platelets, monocytes, macrophages, and several other cell types that was recently demonstrated to be involved in platelet activation in response to oxidized phospholipids, including oxidized LDL. Although the role of CD36 in other vascular cells has not been well defined, previous studies have demonstrated that cd36-knockout (cd36 -/-) mice have prolonged thrombosis times after vascular injury, which can be protective in the state of hyperlipidemia. Here, we found significantly less ROS in the vessel walls of cd36-/- mice compared with WT after chemically induced arterial injury, suggesting that CD36 may contribute to ROS generation in the VSMCs themselves. Gene expression analysis revealed that the antioxidant enzymes peroxiredoxin-2 (Prdx2) and heme oxygenase-1 were upregulated in cd36-/- VSMCs. Molecular dissection of the pathway in isolated mouse VSMCs revealed CD36 ligand-dependent induction of Fyn phosphorylation, with subsequent phosphorylation and degradation of the redox-sensitive transcription factor Nrf2. Chromatin immunoprecipitation experiments further showed that Nrf2 directly occupied the Prdx2 promoter. The importance of this pathway was evidenced by increased ROS generation in prdx2-/- mice and decreased thrombosis times in both prdx2 -/- and nrf2-/- mice after vascular injury. These data suggest that CD36-mediated downregulation of antioxidant systems in VSMCs may contribute to its prothrombotic, proinflammatory, and atherogenic effects.

ISSN 

0021-9738

Link 

http://dx.doi.org/10.1172/JCI42823

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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