title: Do platelet apoptosis, activation, aggregation, lipid peroxidation and platelet-leukocyte aggregate formation occur simultaneously in hyperlipidemia?
abstract: OBJECTIVE
  The circulating lipoproteins may cause some abnormalities in platelet composition and function in hypercholesterolemia. The aim of this study was to investigate whether platelet apoptosis, platelet activation, platelet aggregation, platelet-leukocyte aggregate (PLA) formation and lipid peroxidation occur simultaneously in hyperlipidemia.
  
  
  METHODS
  Expression of GpIIb/IIIa (CD41a), P-selectin (CD62-P), platelet-bound fibrinogen (antifibrinogen), platelet membrane phosphatidylserine (PS), platelet-monocyte aggregates (mono-PLA) and platelet-neutrophil aggregates (neut-PLA) was measured in eight hyperlipidemic and eight normal subjects using flow cytometry. ADP (10 microM) was used to activate platelets. Furthermore, ADP induced platelet aggregation responses, platelet malondialdehyde (MDA) and glutathione (GSH) levels were determined.
  
  
  RESULTS
  Before platelet activation, platelet CD62-P, antifibrinogen, annexin-V, mono-PLA, neut-PLA and platelet MDA levels as well as platelet aggregation responses in the hyperlipidemics were significantly higher than those in the controls (P<0.01, P<0.01, P<0.01, P<0.001, P<0.001, P<0.01, P<0.001, respectively), whereas GpIIb/IIIa expression and GSH levels were not different significantly (P > 0.05). In the control group, CD62-P, antifibrinogen and annexin-V levels increased significantly after ADP activation (P<0.05, P<0.05, P<0.01, respectively). In hyperlipidemic subjects, annexin-V expression increased significantly after activation (P<0.01), whereas expression of GpIIb/IIIa, CD62-P and antifibrinogen remained unchanged (P>0.05). The levels of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), serum fibrinogen (S-FGN) and high density lipoprotein cholesterol (HDL-C) in patients were found to be correlated with platelet CD62-P, antifibrinogen, annexin-V, mono-PLA and MDA.
  
  
  CONCLUSIONS
  In conclusion, it seems that in hyperlipidemia, some platelets are in an activated state in circulation, and that increased lipid peroxidation, early apoptosis, platelet-leukocytes aggregate formation and platelet aggregation altogether accompany this process.
authors.affiliation: Department of Biochemistry, Marmara University Faculty of Pharmacy, Istanbul, Turkey. azizesener@hotmail.com
authors.forename: Azize
authors.initials: A
authors.lastname: Sener
authors.forename: Derya
authors.initials: D
authors.lastname: Ozsavci
authors.forename: Rabia
authors.initials: R
authors.lastname: Oba
authors.forename: Gulderen Yanikkaya
authors.initials: GY
authors.lastname: Demirel
authors.forename: Fikriye
authors.initials: F
authors.lastname: Uras
authors.forename: K Turay
authors.initials: KT
authors.lastname: Yardimci
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology*; D007962:Leukocytes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D019007:P-Selectin / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000096:biosynthesis; D012016:Reference Values
chemical_list: D019007:P-Selectin; D010718:Phosphatidylserines; D019038:Platelet Glycoprotein GPIb-IX Complex; D005340:Fibrinogen; D005978:Glutathione