Distribution of Inflammatory Mediators in Carotid and Femoral Plaques

Abstract

Although atherosclerosis is a known systemic process, carotid and femoral atherosclerotic plaques are associated with distinctive complications and therapeutic outcomes. The purpose of this study was to evaluate inflammatory markers associated with carotid and femoral plaques. Carotid and femoral endarterectomy specimens were harvested from surgical patients. The carotid specimens were further sectioned into central, peripheral, and relatively normal regions. Expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in carotid and femoral specimens were compared and the distributions of MMP-2, MMP-9, and CD40 within the carotid specimens were further analyzed. Messenger RNA (mRNA) levels were measured with real-time polymerase chain reaction and proteins with ELISA assay and Western blot. Despite no significant difference in the MMP-2 mRNA levels between carotid and femoral specimens, the common femoral specimens had significantly lower MMP-2 protein production and higher MMP-9 mRNA and protein expressions than those of the carotid specimens (p = 0.015, p = 0.03, and p = 0.034, respectively). Among carotid specimens, MMP-2 mRNA level was significantly lower in the central region (p < 0.01) and consistent with the distribution pattern of MMP-2 proteins. Interestingly, despite significantly lower MMP-9 mRNA expression in the central region of carotid plaques, active MMP-9 protein level was significantly higher. CD40 mRNA and protein levels were also higher in the central region. Immunohistochemistry analyses showed substantially increased macrophages and CD40 in the central region of the carotid plaques. This study emphasizes that femoral and carotid plaques are distinct entities and that distribution of inflammatory molecular markers varied within these advanced atherosclerotic plaques. Additional analyses are warranted.