Increased RBP4 in a human model of activated anti-atherosclerotic and antiremodelling defences

Abstract

Background: Both increased and decreased levels of the adipokine retinol-binding protein 4 (RBP4) have been reported in cardiovascular disease, and levels of RBP4 have been related to diabetes, metabolic syndrome and cardiovascular risk. Recently, clear in vitro and ex vivo vasodilatory and inhibitory of platelet activation effects of RBP4 has been shown and a reduced RBP4 level was found in high cardiovascular risk patients, suggesting a potential cardiovascular protective role for increased levels of RBP4.

Patients and methods: Plasma level of RBP4 (ELISA) was determined in a cohort of Bartter's and Gitelman's syndrome (BS/GS) patients, a human model of endogenous Ang II signalling antagonism and activation of anti-atherosclerotic and antiremodelling defenses, the opposite of cardiovascular risk patients, and in healthy normotensive subjects. Haem Oxygenase (OH)-1 protein level (sandwich immunoassay) as a potential mediator of RBP4 stimulation of PI3K/Akt pathway and flow-mediated dilation (FMD) as a measure of endothelium (NO)-dependent response have also been measured.

Results: RBP4 in BS/GS patients (40·59 ± 15·32 μg/mL vs. 25·05 ± 5·56, P = 0·011) along with HO-1 protein levels (9·44 ± 3·09 ng/mL vs. 5·49 ± 1·04, P = 0·003) and FMD (10·52% ± 2·22 vs. 7·99 ± 1·13 P = 0·006) were significantly increased compared with healthy normotensive subjects.

Conclusions: The increase of RBP4 in BS/GS, a human model of endogenous Ang II signalling antagonism and activation of anti-atherosclerotic and antiremodelling defenses, the opposite of cardiovascular risk patient, found in concert with an increased NO-mediated vasodilation and HO-1 levels supports a protective role for this adipokine in vascular protection/cardiovascular risk.

Keywords: Atherosclerosis; HO-1; RBP4; cardiovascular risk; nitric oxide; vascular homeostasis.