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Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis

J Clin Invest. 2022-07; 
Wenli Liu, Nataliya Östberg, Mustafa Yalcinkaya, Huijuan Dou, Kaori Endo-Umeda, Yang Tang, Xintong Hou, Tong Xiao, Trevor P Fidler, Sandra Abramowicz, Yong-Guang Yang, Oliver Soehnlein, Alan R Tall, Nan Wang
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Recombinant Proteins … Where indicated, EPO (Genscript, Z02975) was injected 3 … clonal hematopoiesis mice were ip injected 3 times per week with … The mice were ip injected with LDLR ASO once a week at a … Get A Quote

摘要

Elevated hematocrit is associated with cardiovascular risk; however, the causality and mechanisms are unclear. The JAK2V617F (Jak2VF) mutation increases cardiovascular risk in myeloproliferative disorders and in clonal hematopoiesis. Jak2VF mice with elevated WBCs, platelets, and RBCs display accelerated atherosclerosis and macrophage erythrophagocytosis. To investigate whether selective erythroid Jak2VF expression promotes atherosclerosis, we developed hyperlipidemic erythropoietin receptor Cre mice that express Jak2VF in the erythroid lineage (VFEpoR mice). VFEpoR mice without elevated blood cell counts showed increased atherosclerotic plaque necrosis, erythrophagocytosis, and ferroptosis. Selective induction... More

关键词

Atherosclerosis, Vascular Biology