Abstract 150: Carotid Artery Atherosclerosis: Biomarkers of Plaque Instability

Abstract

To identify intraplaque and plasma biomarkers of carotid atherosclerotic plaque instability. We hypothesized that comparison of plaques and plasma from symptomatic and asymptomatic patients would show differences in proteolytic and inflammatory proteins, identifying them as potential markers of an unstable plaque. 42 symptomatic and asymptomatic patients (22 women, 20 men, 52-89 years) presenting for carotid endarterectomy had blood samples drawn and carotid plaques processed for protein extraction. The intraplaque expression of proteolytic enzymes (uPA, tPA, PAI-1 and MMP-2) and inflammatory markers (TF, TSP-1, and TNF-α) were evaluated by Western blot analysis. Plasma analyte concentrations were assayed with LUMINEX CVD1 and Cytokine panels using LUMINEX technology. Intraplaque expression of tPA and uPA was 5.9x and 4.5x higher (n=15, p< .05) respectively in the symptomatic group when compared to the asymptomatic group. The symptomatic group also demonstrated a 4.3x increase in active MMP-2 and a 3.6x increase in PAI-1 expression. Investigation of inflammatory proteins demonstrated 2.7-, 4.7-, and 3.3-fold increases in the expression of TNF- α, TSP-1, and TF, respectively. Plasma levels of MPO, MMP-9, IL8, MCP-1 and TNFα were significantly elevated in both the symptomatic and asymptomatic groups when compared to healthy controls (n=7, p<0.05). While there was no change in ICAM-1 levels between asymptomatic patients and healthy controls, symptomatic patients demonstrated a 35% decrease (n=7, p<0.05) when compared to controls. Also, plasma PAI-1 levels in asymptomatic patients were 55% lower than in symptomatic patients and 75% lower than in healthy controls. Elevated expression of certain inflammatory markers and proteolytic enzymes in carotid plaques was demonstrated in symptomatic patients. Marked differences were also observed in ICAM-1 and PAI-1 expression in the plasma of symptomatic patients relative to asymptomatic patients and healthy controls. This leaves promising avenues for further inquiry into the roles of these proteins in atherosclerotic disease and their potential as clinical biomarkers of an unstable atherosclerotic plaque.