Abstract 497: Sex Differences in the Relationship Between Pro-Inflammatory Adipokines, Chemerin and Resistin, and Carotid Atherosclerotic Plaque Instability

Abstract

Introduction: Sex differences in plaque morphology and composition exist; men develop more unstable plaques than women. Yet, stroke kills more women than men. Despite these differences, no sex-specific guidelines for carotid disease management exist. Thus, markers that reflect sex-specific morphological features in the plaque should be explored for better prediction of stroke risk. Pro-inflammatory adipokines, chemerin and resistin, influence vascular function. Herein we are the first to investigate sex differences in the relationship between carotid plaque instability and the expression of these adipokines. Methods: Subjects with ≥50% carotid stenosis scheduled for a carotid endarterectomy were recruited from McGill-affiliated hospitals. Pre-operative plasma chemerin and resistin levels were measured using ELISA. Stability of carotid plaque specimens was assessed by two gold standard histological classifications. Stable and unstable plaques were immunostained for chemerin, chemerin’s receptor (ChemR23), and resistin. Digital and semi-quantifications assessed the % area of expression as well as staining intensity (mild to high) and % of positively stained macrophages/foam cells. Plaque mRNA expression was assessed by quantitative PCR. Sex-hormone analyses are ongoing. Results: Men (n=171) had more unstable plaque features, i.e., greater hemorrhage (P=0.022), lipid core size (P<0.001), inflammation (P=0.007), cap infiltration (P=0.006), and less fibrous tissue (P<0.001) than women (n=79). Circulating chemerin and resistin levels were similar between men and women and no sex differences were observed in relation to plaque instability. The % area of chemerin and resistin staining in the plaque was greater in unstable vs stable plaques in men only (P=0.040; P=0.005, respectively). Similarly, greater intensity in chemerin, ChemR23, and resistin staining was associated with plaque instability in men only (P<0.001; P=0.013; P=0.033, respectively). In contrast, lower resistin plaque mRNA expression was associated with plaque instability in women only (P=0.040). Conclusion: Our results suggest the possibility of a sex-dependent regulatory mechanism underlying the connection between these adipokines and plaque instability.