Mechanism of collagen-induced platelet aggregation in patients with impaired carbohydrate tolerance or type 2 diabetes mellitus in combination with arterial hypertension

Introduction. Cardiovascular diseases are increasingly associated with pathologies, such as impaired glucose tolerance and type 2 diabetes mellitus (T2DM). This combination causes several negative phenomena in the body, increasing the likelihood of thrombotic complications and negatively affecting the overall prognosis of the diseases. Platelets are closely related to the onset and spread of thrombosis.Objective. To study collagen-induced platelet aggregation and to elucidate the mechanism of action through the cyclic adenosine monophosphate (cAMP)-dependent signaling system in patients with impaired carbohydrate tolerance or T2DM in combination with hypertension.Material and Methods. A cross-sectional study was conducted. The study included 37 patients with hypertension and metabolic disorders aged 40-65 years and 20 healthy volunteers. Serum parameters of carbohydrate metabolism (glucose and glycosylated hemoglobin) were quantitatively determined by the immunoturbidimetric method. Platelet aggregation activity was investigated by turbidimetry with a two-channel laser analyzer. The degree and the rate of platelet aggregation in platelet-rich plasma were determined based on the curves of light transmission and platelet aggregate mean size in the presence of collagen. Intracellular concentrations of cAMP in platelets were increased by preincubation with adenylate cyclase activator, Forskolin (Sigma), and phosphodiesterase type 3 and 5 inhibitor, 3-isobutyl-1-methylxanthine (Sigma), at final concentrations of 100 -m for 30 min.Results. An increase in collagen-induced platelet aggregation and size increase of platelet aggregates were observed in patients with impaired carbohydrate tolerance in combination with hypertension. The correlation relationships were detected between the level of glycosylated hemoglobin, degree of platelet aggregation, and size of platelet aggregates in patients of two groups. The correlation relationships were also detected between the size of platelet aggregates and the duration of the disease in patients with type 2 diabetes in combination with hypertension.Conclusions. The obtained results suggest a dysregulation in the cAMP-mediated signaling system associated with chronic hyperglycemia in study patients.