Enhancement of platelet aggregation by low-density lipoproteins from IDDM patients.
Low-density lipoprotein (LDL) is known to enhance platelet sensitivity to some aggregating agents. In this study, we observed that LDL isolated from patients with insulin-dependent diabetes mellitus (IDDM) enhanced thrombin-induced platelet aggregation to a greater extent than LDL isolated from matched controls (P less than .01). Thromboxane B2 production during aggregation was also significantly more enhanced by LDL isolated from IDDM than by control LDL (P less than .01). There was no difference in the lipid composition (free and esterified cholesterol, total phospholipids, and triglycerides) of LDL isolated from diabetic and control subjects. In contrast, the extent of glycosylation of LDL isolated from diabetic patients was significantly greater than that observed in LDL from normal subjects (P less than .01), and a positive correlation (r = .605, P less than .01) between the degree of LDL glycosylation and the rate of platelet aggregation was observed. LDL glycosylated in vitro enhanced thrombin-, collagen-, and adenosine 5'-diphosphate-induced platelet aggregation to a greater extent than control LDL (P less than .01). Although LDL glycosylated in vitro was taken up by platelets to a greater extent than control LDL (P less than .05), the lipid composition (free cholesterol and phospholipid) of platelets was not significantly changed. We postulate that an increased degree of glycosylation of LDL may enhance its uptake by platelets and lead to increased platelet reactivity to aggregating agents, probably by altering the structure of the platelet membrane. The enhancement of platelet aggregation by LDL may contribute to the accelerated development of atherosclerosis in diabetes mellitus.
Watanabe
J
J
Veterans Administration Medical Center, Charleston, South Carolina.
Wohltmann
H J
HJ
Klein
R L
RL
Colwell
J A
JA
Lopes-Virella
M F
MF
D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D010743:Phospholipids / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000096:biosynthesis
D008077:Lipoproteins, LDL; D010743:Phospholipids; D013929:Thromboxane B2