Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects

Abstract

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.