Abstract 653: Flow-Dependent Accumulation of Inflammatory Cells in the Upstream Shoulder of Atherosclerotic Plaques
Background - An important feature for the progression of atherosclerotic plaques is the presence of inflammation. Disturbed flow conditions were shown to influence the expression of adhesion molecules and the release of chemokines from endothelial cells, thereby inducing the recruitment of circulating immune cells. Thus, we analyzed the frequency of different immune cells, HLA-DR, chemokines, and chemokine receptors in atherosclerotic carotid plaques dependent on the flow direction.
Methods - Carotid endarterectomy specimens of 54 patients were examined in the longitudinal direction. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect and count smooth muscle cells (actin+), immune cells such as macrophages (CD68+), T cells (CD3+), dendritic cells (DCs: fascin+), and mature DCs (CD83+). The expression of HLA-DR, of chemokine receptors (CCR-2, CCR-6), and of chemokines (MCP-1, MIP-3a) was analyzed. The results were compared between the upstream and the downstream plaque shoulder.
Results - Compared to upstream, significantly higher numbers of smooth muscle cells were detected downstream (p < 0.001). In contrast, higher numbers of macrophages (p = 0.01), T cells (NS), DCs (p = 0.03), and mature DCs (p = 0.007) were observed in the upstream than the downstream shoulder. A higher expression of HLA-DR (p = 0.004), CCR-2 (p = 0.002), CCR-6 (p < 0.001), MCP-1 (p = 0.05), and MIP-3a (NS) was detected upstream. Upstream, a significant correlation was detected between macrophages and HLA-DR (r = 0.53, p <0.001) or CCR-2 (r = 0.27, p = 0.05), and between DCs and MIP-3a (r = 0.38, p = 0.007). Downstream, smooth muscle cells significantly correlated with HLA-DR (r = 0.4, p = 0.003). The emergence of immune cells and expression of HLA-DR, chemokines, and chemokine receptors were strongly associated with neovascularization.
Conclusions - Smooth muscle cells expressing HLA-DR are abundant downstream, providing an explanation for the known distal plaque growth. In contrast, the recruitment of macrophages, T cells, and mature DCs, directed by their expression of chemokine receptors responding to local chemokines, through neovessels into the upstream shoulder, might contribute to plaque destabilization by HLA-DR expression.