title: Serum lipid profile determines platelet reactivity to native and modified LDL-cholesterol in humans.
abstract: The effects of thrombin (0.2 U/ml) and native (n-LDL), malondialdehyde-modified (MDA-LDL) and auto-oxidized (ox-LDL) low-density lipoproteins (20 micrograms of protein/ml) on platelet activation were evaluated in seven hyperlipidemic patients and compared to seven controls (fasting serum cholesterol 8.49 +/- 0.5 and 4.61 +/- 0.4 mM, respectively). Basal and thrombin-induced increases in platelet intracellular free calcium ion concentration ([Ca2+]i; fura-2) were similar in hyperlipidemic patients and controls (45 +/- 5 vs 42 +/- 3 and 635 +/- 51 vs 599 +/- 69 mM, respectively). n-LDL, MDA-LDL and ox-LDL increased basal [Ca2+]i (16, 36 and 81 percent, p < 0.01 between LDL-types), increases were consistently smaller in patients. There was an inverse relationship between LDL-induced responses and fasting serum LDL cholesterol as well as LDL/HDL ratio. In conclusion, modified LDL activated platelets to a greater extent than n-LDL, suggesting different types of LDL-receptors. Their agonistic effect was inversely related to the fasting serum lipid profile, suggesting that blunting of platelet responses to LDL could represent a protective mechanism in hyperlipidemic patients.
authors.affiliation: Department of Medicine, Lipid Clinic, Winnipeg, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Katzman
authors.forename: R
authors.initials: R
authors.lastname: Bose
authors.forename: S
authors.initials: S
authors.lastname: Henry
authors.forename: D L
authors.initials: DL
authors.lastname: McLean
authors.forename: S
authors.initials: S
authors.lastname: Walker
authors.forename: C
authors.initials: C
authors.lastname: Fyfe
authors.forename: Y
authors.initials: Y
authors.lastname: Perry
authors.forename: D
authors.initials: D
authors.lastname: Mymin
authors.forename: P
authors.initials: P
authors.lastname: Bolli
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D008078:Cholesterol, LDL / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D008055:Lipids / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D008875:Middle Aged; D010100:Oxygen / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D012016:Reference Values; D013917:Thrombin / Q000494:pharmacology
chemical_list: D008078:Cholesterol, LDL; D008055:Lipids; D008315:Malondialdehyde; D013917:Thrombin; D010100:Oxygen; D002118:Calcium