ABSTRACT
UNLABELLED: The increased cardiovascular risk in type 2 diabetes mellitus (DM2) is the result of disorders of the immune system, including the enhanced reactivity of monocytes and impaired secretion of inflammatory cytokines. The aim of this study was to analyze the expression of calcium-sensing receptor (CaR) in peripheral blood monocytes of individuals with DM2 and peripheral artery disease (PAD). The study included 88 individuals, among them 37 patients with PAD (group A--atherosclerosis), 27 individuals with DM2 and PAD (group AD--atherosclerosis and diabetes mellitus), and 24 controls (group C--controls). The expression of CaR on isolated peripheral blood monocytes was analyzed at the level of surface protein (CaR(surf)) and mRNA (CaR(mRNA)). Concentrations of pro-inflammatory cytokines were determined by means of ELISA, while the severity of PAD was assessed with Doppler and impedance plethysmography. The expression of CaR(surf) was the highest in the controls (mean 41.27%) and did not differ significantly as compared to individuals from group AD (35.66%); however it was significantly higher than in group A (24.49%). The expression of CaR(surf) was related to the severity of PAD, fasting concentration of glucose, and the concentration of monocyte chemotactic protein (MCP-1). Additionally, significant differences were observed with regards to CaR(mRNA) expression; although, no significant relationships were documented between CaR(mRNA) and laboratory or clinical variables. Different ways of CaR(surf) and CaR(mRNA) expression regulation were associated with the concentration of osteopontin. CONCLUSION: A nearly 1.5-fold higher expression of CaR(surf) on the peripheral blood monocytes of individuals with diabetes and PAD manifests during post-transcription stage and depends on fasting glucose concentration and MCP-1 concentration on one hand, and the severity of PAD on the other.
Subject(s)
Atherosclerosis/blood , Diabetes Mellitus, Type 2/blood , Leukocytes, Mononuclear/metabolism , Receptors, Calcium-Sensing/metabolism , Adult , Aged , Blood Glucose/analysis , Chemokine CCL2/blood , Female , Humans , Male , Middle Aged , Receptors, Calcium-Sensing/geneticsABSTRACT
The role of heat shock proteins and anti-HSP 60/65 antibodies in atherogenesis has been widely described in the literature, but the participation of these molecules in the pathogenesis of diabetic macroangiopathy has not been extensively investigated. 30 patients with type 2 diabetes complicated with macroangiopathy of the lower extremities in the intermittent claudication stage. The control group (n=18) consisted of healthy volunteers of corresponding age. Levels of anti-HSP 60/65 antibodies, von Willebrand factor (vWF) and hsCRP in blood serum were measured. We also assessed static effort based on isometric contraction lasting until full fatigue. In patients with lower limb ischemia in diabetic macroangiopathy, a positive correlation between anti-HSP 60/65 antibodies and von Willebrand factor levels in blood serum was found (R=0.543, p<0.05). Concentrations of anti-HSP 60/65 antibodies were higher than in the control group, but not statistically significant (44.77±55.00 vs. 26.09±13.85; NS). The ongoing disease process contributed statistically significantly to the strength of the quadriceps muscle of the thigh (21.47 vs. 27.82 for the right limb, and 20.27 vs. 28.33 for the left limb; p<0.05). Increased concentrations of anti-HSP 60/65 antibodies in blood serum suggests their involvement in the pathogenesis of diabetic macroangiopathy and correlates with the parameters of endothelial cell damage. In patients with type 2 diabetes complicated with atherosclerotic changes, a statistically significant reduction in lower limb muscle strength was found compared with the control group.
