title: Collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus.
abstract: OBJECTIVE
  We developed a novel method for diagnosing platelet hyper-aggregation in patients with type 2 diabetes mellitus (DM).
  
  
  METHODS
  By measuring the dose response of platelet aggregation to collagen, an individual ED(50) was determined. Based on the normal range identified in non-DM controls (mean+/-two SEM=0.460+/-0.082 microg/ml, n=47), type 2 DM patients were divided into high ED(50) (ED(50)>0.542 microg/ml; n=32: group I) or low ED(50) groups (ED(50)<0.378 microg/ml; n=32; group II). In these patients, collagen-induced levels of phospho-p38 MAPK and phospho-p44/p42 MAPK were measured using Western blots and enzyme-linked immunosorbent assays (ELISA).
  
  
  RESULTS
  In group II, the collagen (0.3 and 1 microg/ml)-induced levels of both phospho-p38 MAPK and phospho-p44/p42 MAPK measured by western blot analysis were found to be significantly higher than those in group I. The individual ED(50) was found to be significantly correlated with the collagen-induced levels of phospho-p38 MAPK and phospho-p44/p42 MAPK. This correlation was also observed when ELISA was used to measure phospho-p38 MAPK levels in a different population of DM patients (n=90).
  
  
  CONCLUSIONS
  These results strongly suggest that the phosphorylation levels of collagen-induced p38 MAPK and p44/p42 MAPK represent the hyperaggregability of platelets and that the quantification of phospho-p38 MAPK can be a new and useful diagnostic biomarker of platelet hyper-aggregation in DM patients.
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Hanai
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yasuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Kato
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Seiko
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D001791:Blood Platelet Disorders / Q000175:diagnosis* / Q000209:etiology*; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases