title: 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.
authors.affiliation: Unitat de Diabetologia, Endocrinologia i Nutricio and Servei de Medicina Interna, University Hospital of Girona Dr Josep Trueta, Girona, Spain. uden.jmfernandezreal@htrueta.scs.es
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: Antoni
authors.initials: A
authors.lastname: Castro
authors.forename: Montserrat
authors.initials: M
authors.lastname: Broch
authors.forename: Georgina
authors.initials: G
authors.lastname: Peñarroja
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Gabriel
authors.initials: G
authors.lastname: Vázquez
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
mesh_terms: D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002097:C-Reactive Protein; D003430:Cross-Sectional Studies; D006152:Cyclic GMP / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation
chemical_list: D018950:Lipopolysaccharide Receptors; D009566:Nitrates; D009573:Nitrites; D002097:C-Reactive Protein; D006152:Cyclic GMP