Altered monocyte calcium-sensing receptor expression in patients with type 2 diabetes mellitus and atherosclerosis.

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.