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


RESULTS
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.


CONCLUSIONS
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.
Dole
Vandana S
VS
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Matuskova
Jana
J
Vasile
Eliza
E
Yesilaltay
Ayce
A
Bergmeier
Wolfgang
W
Bernimoulin
Michael
M
Wagner
Denisa D
DD
Krieger
Monty
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics; D001792:Blood Platelets / Q000473:pathology* / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018110:Receptors, Lipoprotein / Q000235:genetics* / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D013921:Thrombocytopenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D008075:Lipoproteins, HDL; D018110:Receptors, Lipoprotein; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; D000244:Adenosine Diphosphate; D002784:Cholesterol