title: Alterations of platelet biochemical and functional properties in newly diagnosed type 1 diabetes: a role in cardiovascular risk?
abstract: BACKGROUND
  The involvement of platelets in the pathogenesis of diabetic vascular complications is supported by several studies. Type 1 diabetic (T1D) platelets show increased adhesiveness and aggregation related to a modification of nitric oxide synthase activity. Moreover, different cell types from diabetic patients showed a decreased membrane Na(+) /K(+) -ATPase activity, which might be involved in diabetic complications. The aim of this study was to investigate whether T1D at onset is able to induce alterations of platelet physicochemical and functional properties and whether these changes are affected by hyperglycaemia.
  
  
  METHODS
  The study was performed on 50 young subjects: 30 patients (1-14 years) affected by T1D and 20 age- and gender-matched healthy subjects. We analyzed platelet membrane fluidity by fluorescent anisotropy of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene, Na(+) /K(+) -ATPase, nitric oxide, and peroxynitrite production.
  
  
  RESULTS
  In T1D subjects, we observed an increased fluidity in the plasma membrane outer part and greater rigidity in the internal part compared with that in controls. Na(+) /K(+) -ATPase activity and nitric oxide levels were significantly reduced, while peroxynitrite production was increased compared with that in controls. Moreover, correlations found between the above parameters were correlated with fasting glycaemia and haemoglobin A(1c).
  
  
  CONCLUSIONS
  T1D patients exhibit structural and functional modifications of platelet membrane properties and alterations of nitric oxide metabolism due to diabetes per se and not to chronic hyperglycaemia, insulin therapy, or ageing. These results support the hypothesis that oxidative attack could be an important early event in the pathogenesis of diabetic complications.
authors.affiliation: Department of Biochemistry, Biology and Genetics, School of Medicine, Polytechnic University of Marche, Via Ranieri 65, Ancona, Italy. vignini2@libero.it
authors.forename: Arianna
authors.initials: A
authors.lastname: Vignini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Moroni
authors.forename: Laura
authors.initials: L
authors.lastname: Nanetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Raffaelli
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cester
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.forename: Valentino
authors.initials: V
authors.lastname: Cherubini
authors.forename: Laura
authors.initials: L
authors.lastname: Mazzanti
mesh_terms: D000293:Adolescent; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005260:Female; D005454:Fluorescence Polarization; D006801:Humans; D007223:Infant; D008297:Male; D008560:Membrane Fluidity; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology; D012306:Risk; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
chemical_list: D030421:Peroxynitrous Acid; D004161:Diphenylhexatriene; D009569:Nitric Oxide; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D000254:Sodium-Potassium-Exchanging ATPase