Abstract 370: Dendritic Cells Express Triggering Receptor Expressed on Myeloid Cells-1 and Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis

Abstract

Aim: Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates. Immune cells, including T-lymphocytes, dendritic cells (DCs) and macrophages recruited from blood stream into atherosclerotic lesions, are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. Upon activation, DCs, macrophages, and neutrophils produce several inflammatory cytokines and growth factors. In atherosclerotic tissue, the number of DCs increases with the progression of the lesion. In this study, we examined the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in plaque DCs and compared between the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. Methods and Results: Surgical specimens of human atherosclerotic plaques were obtained from patients undergoing carotid endarterectomy. The expression patterns of TREM-1, HLA-DR, and fascin (DC) were determined by immunofluorescence with α-actin as specific marker to identify smooth muscle cells (VSMCs). There was a marked decrease in VSMCs and an increased density of HLA-DR+ cells in the plaques of S than AS patients. Fascin expression to show DCs was undetectable in normal carotid artery specimens but significantly increased in the carotid plaques of S compared to AS. TREM-1 expression was increased in S and localized with HLA-DR and fascin. However, TREM-1 was increased in S plaques containing less number of VSMCs. The mRNA expression of MMP-9, MMP-1 was increased while Col 1 (α1) and Col III (α1) mRNA transcripts were decreased in S plaques. Conclusions: Increased expression of TREM-1 in plaque DCs of S compared to AS patients suggests a potential role of TREM-1 in atherosclerotic plaque vulnerability. Collectively, these data demonstrate that selective blockade of TREM-1 may contribute to the development of new therapies and promising targets for stabilizing atherosclerotic plaques.