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

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.­

Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Huang, R., Guo, G., Lu, L., Fu, R., Luo, J., Liu, Z., Gu, Y., Yang, W., Zheng, Q., Chao, T., He, L., Wang, Y., Niu, Z., Wang, H., Lawrence, T., Malissen, M., Malissen, B., Liang, Y., Zhang, L. Tags: Research Articles Source Type: research