A novel role for CD36 in VLDL-enhanced platelet activation.
Type 2 diabetes is characterized by increased plasma triglyceride levels and a fourfold increase in ischemic heart disease, but the mechanism is unclear. CD36 is a receptor/transporter that binds fatty acids of lipoproteins. CD36 deficiency has been linked with insulin resistance. There is strong evidence of in vivo interaction between platelets and atherogenic lipoproteins suggesting that atherogenic triglyceride-rich lipoproteins, such as VLDL, that are increased in diabetic dyslipidemia are important in this process. This study demonstrates that VLDL binds to the platelet receptor CD36, enhances platelet thromboxane A2 production, and causes increased collagen-mediated platelet aggregation. VLDL enhanced collagen-induced platelet aggregation by 1) shortening the time taken for aggregation to begin (lag time) to 70% of control (P = 0.001); 2) increasing maximum aggregation to 170% of control (P = 0.008); and 3) increasing thromboxane production to 3,318% of control (P = 0.004), where control represents platelets stimulated with collagen (100%). A monoclonal antibody against CD36 attenuated VLDL-enhanced collagen-induced platelet aggregation by 1) inhibiting binding of VLDL to platelets by 75% (P = 0.041); 2) lengthening lag time to 190% (P < 0.001); and 3) decreasing thromboxane production to 8% of control (P < 0.001). In support of this finding, platelets from Cd36-deficient rats showed no increase in aggregation, thromboxane production, and VLDL binding in contrast to platelets from rats expressing CD36. These data suggest that platelet Cd36 has a key role in VLDL-induced collagen-mediated platelet aggregation, possibly contributing to atherothrombosis associated with increased VLDL levels.
Englyst
Nicola A
NA
Endocrinology and Metabolism Unit, University of Southampton, Southhampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
Taube
Janis M
JM
Aitman
Timothy J
TJ
Baglin
Trevor P
TP
Byrne
Christopher D
CD
D015703:Antigens, CD / Q000097:blood; D018955:CD36 Antigens / Q000097:blood*; D003094:Collagen / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008079:Lipoproteins, VLDL / Q000494:pharmacology / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013928:Thromboxane A2 / Q000097:blood; D014280:Triglycerides / Q000097:blood
D015703:Antigens, CD; D018955:CD36 Antigens; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D013928:Thromboxane A2; D003094:Collagen