Janus kinase 2 (valine to phenylalanine at residue 617) (JAK2 V617F ) mutations lead to myeloproliferative neoplasms associated with elevated myeloid, erythroid, and megakaryocytic cells. Alternatively these same mutations can lead to the condition of clonal hematopoiesis with no impact on blood cell counts. Here, a model of myeloid-restricted JAK2 V617F expression from lineage-negative bone marrow cells was developed and evaluated. This model displayed greater cardiac inflammation and dysfunction following permanent left anterior descending artery ligation and transverse aortic constriction. These data suggest that JAK2 V617F mutations arising in myeloid progenitor cells may contribute to cardiovascular disease by promoting the proinflammatory properties of circulating myeloid cells.
Keywords: AIM2, absence in melanoma 2; ANOVA, analysis of variance; ARCH, age-related clonal hematopoiesis; BMT, bone marrow transplant; CCL2, C-C motif chemokine ligand 2; CHIP, clonal hematopoiesis of indeterminate potential; GFP, green fluorescent protein; HSC, hematopoietic stem cell; HSPC, hematopoietic stem and progenitor cell; IFNGR1, interferon gamma receptor 1; IL, interleukin; JAK2, Janus kinase 2; JAK2V617F, mutant Janus kinase 2 (valine to phenylalanine at residue 617); JAK2WT, wild-type Janus kinase 2; LPS, lipopolysaccharide; LT-HSC, long-term hematopoietic stem cell; MI, myocardial infarction; MPN, myeloproliferative neoplasm; NET, neutrophil extracellular traps; STAT, signal transducer and activator of transcription; TAC, transverse aortic constriction surgery; clonal hematopoiesis; left ventricular hypertrophy; myocardial infarction.
© 2019 The Authors.