[Aggregation of human blood platelets by remnant-like lipoprotein particles].
The action of lipoprotein lipase on chylomicrons (CM) and very low density lipoproteins (VLDL) produces remnant lipoproteins (RLP) that are rich in triglycerides, cholesterol and apolipoprotein E (apo E). Apo E serves as a ligand for the LDL receptor and mediates uptake of RLP by macrophages, vascular wall and other cells that express the LDL receptor. Uptake of RLP can profoundly alter the physiology of cells and promote atherosclerosis and thrombosis. Like RLP, blood platelets also have roles in atherosclerosis and thrombosis; hence it is likely that RLP can influence platelet activity as well. Platelet aggregation was assessed by measuring the loss of single platelets. Apo E3/3-rich RLP derived from normal human plasma VLDL and CM were prepared by an immunoseparation method. At 2.5 to 10 microliters, RLP induced platelet aggregation that increased with the dose of RLP, but decreased it at 25 to 200 microliters. Unlike apo E3/3-rich RLP, apo E4/3 (heterozygous phenotype) rich RLP caused platelet aggregation in a dose-dependent manner, without producing a bell-shape dose-response relationship. Scanning electron microscopy revealed that activated platelets had adhered to and formed aggregates on the red cell membrane. The platelet response was unaffected by aspirin, but was inhibited by apyrase (an ADP scavenger), 2-chloroadenosine (a platelet ADP-receptor antagonist) and cilostazol, a phosphodiesterase type III inhibitor. It is thought that RLP cause leakage of ADP from red cells, which then mediates platelet aggregation.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamastu 431-3192, Japan. umemura@hama-med.ac.jp
Saniabadi
A R
AR
D000244:Adenosine Diphosphate / Q000097:blood / Q000502:physiology; D001053:Apolipoproteins / Q000494:pharmacology* / Q000502:physiology; D001057:Apolipoproteins E / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000502:physiology; D002784:Cholesterol; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000502:physiology; D006801:Humans; D008024:Ligands; D008074:Lipoproteins / Q000494:pharmacology* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology* / Q000502:physiology
D001053:Apolipoproteins; D001057:Apolipoproteins E; D008024:Ligands; D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D000244:Adenosine Diphosphate; D002784:Cholesterol