Abstract TP433: Free Leptin And Soluble Leptin Receptor: Novel Circulating Markers Of Carotid Plaque - Related Symptomatology And Potential Role In Plaque Stability (from The Opal-lille Carotid Endarterectomy Study)

Abstract

Leptin, an adipocyte-derived cytokine with various effects on the cardiovascular system, circulates in a free biologically active form and a bound form to a soluble leptin receptor (sObR) involved in modulating leptin activity. The links between free leptin, sObR, human atherosclerotic carotid plaque phenotype remain unknown. In the present study, we investigated the potential links between serum/plaque free leptin, serum sObR, carotid plaque stability and related symptomatology in 146 consecutive patients (71 asymptomatic and 75 symptomatic) scheduled for carotid endarterectomy. Free leptin was assessed in serum (17.05±23.19 ng/mL, range 0.47-191) and carotid plaques (0.204±0.486 ng/mg protein) and sObR in serum (21.48±8.81 ng/ml). Serum free leptin concentrations were correlated negatively with serum sObR concentrations and positively with intra-plaque free leptin concentrations (p<0.0001, r=0.491, p<0.0001, r=0.726, respectively). Serum free leptin and sObR concentrations were independently associated with carotid artery symptomatology (ß=--0.048; 95%CI [-0.093;-0.002]; -0.102, 95% CI [-0.994;-0.026], respectively). Regarding plaque phenotype, histological examination of carotid endarterectomy specimens revealed plaque stability index (collagen to macrophages area ratio) and Vascular Smooth Muscle Cell (VSMC) content to be significantly higher in asymptomatic patients compared to symptomatic ones (2.1 (1.9-2.5) vs. 1.5 (1.1-1.8), p< 0.0001; 39.2 (35.9-55.0) vs. 20.4 (17.8-26.3), p= 0.0003, respectively). When serum or plaque leptin levels were above median value, plaque stability index, plaque VSMC content, plaque VSMC proliferation index and ERK activation were significantly higher (p< 0.02). Interestingly, via ERK pathway activation, at 20 ng/mL, leptin induced a migratory signal and higher collagen synthesis in human VSMC, followed by a proliferative response of VSMC at the concentration of 75 ng/mL. For the first time, we reported free leptin and sObR to be novel circulating markers of carotid plaque - related symptomatology. Free leptin could be an active player in carotid plaque stability via its effects on human VSMC.