High density lipoprotein modulates platelet function.
BACKGROUND
Platelet activation by atherogenic lipoproteins can be antagonized by high density lipoprotein (HDL), probably via interaction with the ATP-binding cassette transporter A1 (ABCA1).


METHODS
ABCA1 expression and its association with cholesterol rich membrane domains was analyzed by mRNA and Western blot analysis. HDL effects on platelet receptor clustering were analyzed by flow cytometric analysis of fluorescence resonance energy transfer between fluorochrome-labeled antibodies.


RESULTS
ABCA1 expression increased upon megakaryocytic differentiation of human stem cells and ABCA1 protein partially associated to LubroIWX-resistant membrane domains. Plasma HDL-cholesterol in healthy donors negatively correlated to the platelet membrane cholesterol content. Receptor cluster analysis revealed a decrease in the association of Gplb and FcgammaRII upon incubation of platelets with HDL3.


CONCLUSIONS
Our results suggest that HDL modulates platelet reactivity by altering lipid raft associated receptor clustering.
Barlage
Stefan
S
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
Boettcher
Dorothee
D
Boettcher
Alfred
A
Dada
Ashraf
A
Schmitz
Gerd
G
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D039661:Integrin beta3 / Q000032:analysis; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D053440:Lipoproteins, HDL3; D008533:Megakaryocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins; D021962:Membrane Microdomains / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018952:Antigens, CD34; D039661:Integrin beta3; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb; D012333:RNA, Messenger; D017452:Receptors, IgG; C094990:adhesion receptor