Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

摘要

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P = .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29in patients with complications and 0.21 ± 0.18 in patientswithout complications (P = .003). Stimulation resulted ina nonsignificant increase in both groups. Basal TF activity(U/10⁶ PBMCs) was 18.4 ± 13.2 in patients with complicationsand 6.96 ± 5.2 in patients without complications (P =.003). It increased 3-fold in both groups after stimulation(P = .001). TF antigen (pg/10⁶ PBMCs) was 33.7 ± 28.6 inpatients with complications, 10.4 ± 7.8 in patients without complications (P = .02). Stimulation tripled TF antigen inboth groups of patients (P = .001). The RAGE/TF axis isup-regulated inT2Dpatients with vascular complications ascompared to patients without complications. This suggestsa role for this axis in the pathogenesis of vascular complicationsin T2D.