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Cardiovascular disease

Cardiovascular disease

ATP-binding cassette sub-family G member 4 (ABCG4); lyn kinase (LYN); thrombopoietin receptor (CD110; Mpl)

Cell culture and mouse studies suggest activating LYN or increasing high-density lipoprotein (HDL) levels could reduce platelet production and help prevent thrombocytosis. In mice with accelerated development of thrombocytosis from lack of Abcg4, bone marrow megakaryocyte progenitors produced more platelets and had greater cell surface Mpl expression than progenitors from wild-type mice. In wild-type mice with hypercholesterolemia, infusion of HDL decreased megakaryocyte progenitor proliferation, platelet counts and cell-surface Mpl expression compared with vehicle. In megakaryocyte progenitor cells lacking Abcg4, a small molecule LYN activator decreased Mpl expression compared with vehicle. Next steps include testing the effect of LYN activation and HDL infusion in additional mouse models.

SciBX 6(16); doi:10.1038/scibx.2013.390
Published online April 25, 2013

Patent application filed; available for licensing

Murphy, A.J. et al. Nat. Med.; published online April 14, 2013;
Contact: Nan Wang, Columbia University, New York, N.Y.