JACC: Basic to Translational Science (Oct 2019)

JAK2V617F-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure

  • Soichi Sano, MD, PhD,
  • Ying Wang, MD, PhD,
  • Yoshimitsu Yura, MD, PhD,
  • Miho Sano, MD, PhD,
  • Kosei Oshima, MD, PhD,
  • Yue Yang, PhD,
  • Yasufumi Katanasaka, PhD,
  • Kyung-Duk Min, MD, PhD,
  • Shinobu Matsuura, DVM, PhD,
  • Katya Ravid, DSc,
  • Golam Mohi, PhD,
  • Kenneth Walsh, PhD

Journal volume & issue
Vol. 4, no. 6
pp. 684 – 697

Abstract

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Summary: Janus kinase 2 (valine to phenylalanine at residue 617) (JAK2V617F) 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 JAK2V617F 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 JAK2V617Fmutations arising in myeloid progenitor cells may contribute to cardiovascular disease by promoting the proinflammatory properties of circulating myeloid cells. Key Words: clonal hematopoiesis, left ventricular hypertrophy, myocardial infarction