Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe^-/- Mice.

ABSTRACT:

Objective

Increased myelopoiesis has been linked to risk of atherosclerotic cardiovascular disease (ACD). Excessive myelopoiesis can be driven by dyslipidemia and cholesterol accumulation in hematopoietic stem and progenitor cells (HSPC) and may involve increased signaling via Janus kinase 2 (JAK2). Constitutively activating JAK2 mutants drive biased myelopoiesis and promote development of myeloproliferative neoplasms (MPN) or clonal hematopoiesis, conditions associated with increased risk of ACD. JAK2 inhibitors have been developed as a therapy for MPNs. The potential for JAK2 inhibitors to protect against atherosclerosis has not been tested. We therefore assessed the impact of JAK2 inhibition on atherogenesis.

Methods

A selective JAK2 inhibitor TG101348 (fedratinib) or veh

SUBMITTER: Tang Y 

PROVIDER: S-EPMC7125070 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature