mRNA expression of platelet activating factor receptor (PAFR) in peripheral blood mononuclear cells is associated with albuminuria and vascular dysfunction in patients with type 2 diabetes.

AIMS

Renal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM).

METHODS

We recruited 95 patients with T2DM. After matching for gender, age, BMI and HbA1c levels, the patient cohort included 42 with normoalbuminuria, 28 with microalbuminuria, and 25 with macroalbuminuria. All patients in the three groups were assessed for urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), flow-mediated dilatation (FMD), and mRNA expression in PBMCs.

RESULTS

The mRNA expression of platelet activating factor receptor (PAFR) differed most markedly between the three groups and was significantly higher in the macroalbuminuric group (p < 0.001 vs. normoalbuminuric group; p < 0.05 vs. microalbuminuric group). PAFR mRNA expression significantly correlated with log transformed ACR (ρ = 0.424, p < 0.001) but not eGFR. PAFR mRNA expression also had a significant negative correlation with FMD (ρ = -0.379, p < 0.001). Furthermore, the prevalence of macrovascular complications, particularly stroke, was significantly higher in patients with elevated PAFR mRNA expression in PBMCs.

CONCLUSIONS

PAFR overexpression in PBMCs may link diabetic nephropathy to macroangiopathy through impairment of endothelial function in patients with T2DM.