AIMS: We developed a novel method for diagnosing platelet hyper-aggregation in patients with type 2 diabetes mellitus (DM). MAIN 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). KEY FINDINGS: 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). SIGNIFICANCE: 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.
AIMS: We developed a novel method for diagnosing platelet hyper-aggregation in patients with type 2 diabetes mellitus (DM). MAIN 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 DMpatients 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-p38MAPK and phospho-p44/p42 MAPK were measured using Western blots and enzyme-linked immunosorbent assays (ELISA). KEY FINDINGS: In group II, the collagen (0.3 and 1 microg/ml)-induced levels of both phospho-p38MAPK 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-p38MAPK and phospho-p44/p42 MAPK. This correlation was also observed when ELISA was used to measure phospho-p38MAPK levels in a different population of DMpatients (n=90). SIGNIFICANCE: These results strongly suggest that the phosphorylation levels of collagen-induced p38MAPK and p44/p42 MAPK represent the hyperaggregability of platelets and that the quantification of phospho-p38MAPK can be a new and useful diagnostic biomarker of platelet hyper-aggregation in DMpatients.
Authors: Michelle Kiebala; Meera V Singh; Michael S Piepenbrink; Xing Qiu; James J Kobie; Sanjay B Maggirwar Journal: PLoS One Date: 2015-06-15 Impact factor: 3.240