JAK2-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure

Abstract

Janus kinase 2 (valine to phenylalanine at residue 617) (<i>JAK2</i> ^<i>V617F</i> ) 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 <i>JAK2</i> ^<i>V617F</i> 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 <i>JAK2</i> ^<i>V617F</i> mutations arising in myeloid progenitor cells may contribute to cardiovascular disease by promoting the proinflammatory properties of circulating myeloid cells.