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Article Dans Une Revue Journal of Lipid Research Année : 2019

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

Rong Huang
  • Fonction : Auteur
Guo Guo
  • Fonction : Auteur
Liaoxun Lu
  • Fonction : Auteur
Rui Fu
  • Fonction : Auteur
Zhuangzhuang Liu
  • Fonction : Auteur
Yanrong Gu
  • Fonction : Auteur
Wenyi Yang
  • Fonction : Auteur
Qianqian Zheng
  • Fonction : Auteur
Tianzhu Chao
  • Fonction : Auteur
Le He
Zhiguo Niu
  • Fonction : Auteur
Toby Lawrence
Marie Malissen
Bernard Malissen
Yinming Liang
Lichen Zhang

Résumé

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.-

Domaines

Immunologie

Dates et versions

hal-02475041 , version 1 (11-02-2020)

Identifiants

Citer

Rong Huang, Guo Guo, Liaoxun Lu, Rui Fu, Jing Luo, et al.. The three members of the Vav family proteins form complexes that concur to foam cell formation and atherosclerosis[S]. Journal of Lipid Research, 2019, 60 (12), pp.2006-2019. ⟨10.1194/jlr.M094771⟩. ⟨hal-02475041⟩
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