Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils.

ABSTRACT: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2^V617F) mice, as well as recipient mice transplanted with JAK2^V617F bone marrow cells. JAK2V617F progressively upregulates A

SUBMITTER: Kimishima Y 

PROVIDER: S-EPMC8548396 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature