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Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice.

ABSTRACT: High-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediated cellular uptake of lipoprotein cholesterol controls HDL structure and plasma HDL and biliary cholesterol levels. In SR-BI knockout (KO) mice, an unusually high plasma unesterified-to-total cholesterol ratio (UC:TC) and abnormally large HDL particles apparently contribute to pathology, including female infertility, susceptibility to atherosclerosis and coronary heart disease, and anemia. Here we examined the influence of SR-BI deficiency on platelets.The high plasma UC:TC ratio in SR-BI KO mice was correlated with platelet abnormalities, including high cholesterol content, abnormal morphologies, high clearance rates, and thrombocytopenia. One day after platelets from wild-type mice were infused into SR-BI KO mice, they exhibited abnormally high cholesterol content and clearance rates similar to those of endogenous platelets. Platelets from SR-BI KO mice exhibited in vitro a blunted aggregation response to the agonist ADP but a normal response to PAR4.In SR-BI KO mice abnormal circulating lipoproteins, particularly their high UC:TC ratio-rather than the absence of SR-BI in platelets themselves-induce defects in platelet structure and clearance, together with a mild defect in function.

SUBMITTER: Dole VS

PROVIDER: S-EPMC2683374 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice.

Dole Vandana S VS Matuskova Jana J Vasile Eliza E Yesilaltay Ayce A Bergmeier Wolfgang W Bernimoulin Michael M Wagner Denisa D DD Krieger Monty M

Arteriosclerosis, thrombosis, and vascular biology 20080424 6

<h4>Objective</h4>High-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediated cellular uptake of lipoprotein cholesterol controls HDL structure and plasma HDL and biliary cholesterol levels. In SR-BI knockout (KO) mice, an unusually high plasma unesterified-to-total cholesterol ratio (UC:TC) and abnormally large HDL particles apparently contribute to pathology, including female infertility, susceptibility to atherosclerosis and coronary heart disease, and anemia ...[more]

PMID: 18436807

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Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice.

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Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice.

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