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• W2893157370 abstract "Thrombocytopenia in scavenger receptor BI (SR-BI) knockout mice is suggested to result from augmented platelet clearance induced by elevated intracellular unesterified cholesterol (UC) levels. We hypothesize that SR-BI deficiency may also influence platelet production at the level of its precursor cell in the bone marrow, the megakaryocyte.In this study, we compared megakaryopoiesis and platelet production in SR-BI knockout and wild-type mice.In line with our hypothesis, megakaryocytes from SR-BI knockout mice exhibited UC accumulation while no accumulation of UC was detectable in wild-type megakaryocytes. Bone marrow expression of transcription factors involved in megakaryocyte maturation was induced, but megakaryocyte counts were unchanged in bone marrow of SR-BI knockout mice. Interestingly, we did find a striking 62% decrease (p < 0.01) in proplatelet production by SR-BI knockout megakaryocytes. SR-BI knockout mice displayed an impaired increase in circulating platelet concentrations and bone marrow megakaryocyte numbers upon thrombopoietin challenge. Importantly, megakaryocytes from normolipidemic bone marrow-specific SR-BI knockout mice exhibited a normal ability to produce proplatelets. Moreover, bone marrow-specific deletion of SR-BI did not impair the thrombopoietin response or induce thrombocytopenia, confirming that absence of megakaryocyte SR-BI does not underlie the thrombocytopenic phenotype in total body SR-BI knockout mice.In conclusion, the elevation of plasma unesterified cholesterol levels impairs megakaryopoiesis and platelet production in SR-BI knockout mice. Our findings suggest that, in addition to an increased platelet clearance, a decrease in platelet production may also, in part, explain the thrombocytopenic phenotype associated with SR-BI deficiency in mice." @default.
• W2893157370 created "2018-10-05" @default.
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• W2893157370 date "2019-03-01" @default.
• W2893157370 modified "2023-09-24" @default.
• W2893157370 title "Hypercholesterolemia impairs megakaryopoiesis and platelet production in scavenger receptor BI knockout mice" @default.
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• W2893157370 doi "https://doi.org/10.1016/j.atherosclerosis.2018.09.019" @default.
• W2893157370 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30278990" @default.
• W2893157370 hasPublicationYear "2019" @default.
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