RANK-L is a Potential Therapeutic Target in Homogeneous Atherosclerotic Plaques

Abstract

Objective and design: The late stages of carotid atherosclerosis are responsible for increased local stiffness, suggesting the need for a therapeutic target that affect either plaque composition and arterial stiffness. There is a lack of data on the role of the local arterial stiffness, assessed by radio-frequency based system and its relationship with the molecular profile of plaques. Subjects: In this study we enrolled 18 consecutive patients undergoing carotid endoarterectomy, with homogeneus or heterogeneous plaques, as established by Doppler-ultrasound and local pulse-wave velocity was assessed before surgery. Methods: In carotid plaque specimens, we evaluated inflammasome (NLRP3), Receptor Activator of Nuclear Factor κB (RANK) and its natural ligand (RANK-L), Osteoprotegerin (OPG), and other inflammatory and apoptotic molecules by Western Blotting and qPCR analysis. In addition, lipid peroxidation of arterial specimens was assessed by TBARS assay. Results: In heterogeneus plaques we observed increased OPG expression (p=0.04), positively correlated with lipid peroxidation values (r=0.511, p=0.03); increased levels of RANK (p=0.02), and other inflammatory and apoptotic molecules. RANK-L protein was augmented in homogeneus plaques (p=0.01) and correlated to s-index (r=0.514, p=0.03) and PWV (r=0.525, p=0.03) values. Conclusions: Our data provide evidence that increased local PWV and s-index might identify plaque evolution towards calcification.