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

José-Manuel Fernández-Real; Abel López-Bermejo; Antoni Castro; Montserrat Broch; Georgina Peñarroja; Joan Vendrell; Gabriel Vázquez; Wifredo Ricart

doi:10.1160/th04-12-0831

PubMed · 16268480

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

José-Manuel Fernández-Real·Abel López-Bermejo·Antoni Castro·Montserrat Broch·Georgina Peñarroja·Joan Vendrell·Gabriel Vázquez·Wifredo Ricart

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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.

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Brachial Artery C-Reactive Protein Cross-Sectional Studies Cyclic GMP Diabetes Mellitus, Type 2 Endothelium, Vascular Female Humans Lipopolysaccharide Receptors Male Nitrates Nitrites Ultrasonography Vasodilation Comparative Study Journal Article Research Support, Non-U.S. Gov't

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José-Manuel Fernández-Real, Abel López-Bermejo, Antoni Castro, Montserrat Broch, Georgina Peñarroja, Joan Vendrell, Gabriel Vázquez, Wifredo Ricart. 2005. Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects.. https://doi.org/10.1160/th04-12-0831

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