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The three members of the Vav family proteins form complexes that concur to foam cell formation and atherosclerosis

Research output: Contribution to journalArticle

Rong Huang, Guo Guo, Liaoxun Lu, Rui Fu, Jing Luo, Zhuangzhuang Liu, Yanrong Gu, Wenyi Yang, Qianqian Zheng, Tianzhu Chao, Le He, Ying Wang, Zhiguo Niu, Hui Wang, Toby Lawrence, Marie Malissen, Bernard Malissen, Yinming Liang, Lichen Zhang

Original languageEnglish
Pages (from-to)2006-2019
Number of pages14
JournalJournal of Lipid Research
Volume60
Issue number12
DOIs
Publication statusPublished - 1 Jan 2019

King's Authors

Abstract

During foam cell formation and atherosclerosis development, the scavenger receptor CD36 plays critical roles in lipid uptake and triggering of atherogenicity via the activation of Vav molecules. The Vav family includes three highly conserved members known as Vav1, Vav2, and Vav3. As Vav1 and Vav3 were found to exert function in atherosclerosis development, it remains thus to decipher whether Vav2 also plays a role in the development of atherosclerosis. In this study we found that Vav2 deficiency in RAW264.7 macrophages significantly diminished oxidized LDL uptake and CD36 signaling, demonstrating that each Vav protein family member was required for foam cell formation. Genetic disruption of Vav2 in ApoE-deficient C57BL/6 mice significantly inhibited the severity of atherosclerosis. Strikingly, we further found that the genetic deletion of each member of the Vav protein family by CRISPR/Cas9 resulted in a similar alteration of transcriptomic profiles of macrophages. The three members of the Vav proteins were found to form complexes, and genetic ablation of each single Vav molecule was sufficient to prevent endocytosis of CD36. The functional interdependence of the three Vav family members in foam cell formation was due to their indispensable roles in transcriptomic programing, lipid uptake, and activation of the JNK kinase in macrophages.

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