Collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus.
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.
Hanai
Yoshiteru
Y
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Adachi
Seiji
S
Yasuda
Ichiro
I
Takai
Shinji
S
Matsushima-Nishiwaki
Rie
R
Kato
Hisaaki
H
Enomoto
Yukiko
Y
Akamatsu
Shigeru
S
Sakakibara
Seiko
S
Ogura
Shinji
S
Iwama
Toru
T
Kozawa
Osamu
O
Tokuda
Haruhiko
H
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*
D015415:Biomarkers; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases