Monocyte chemoattractant protein-1 in human atheromatous plaques.

TLDR

Monocytes are central to atherogenesis, yet the chemotactic signals that recruit them to human atheroma are poorly understood, and monocyte chemoattractant protein‑1 (MCP‑1) is a potent chemokine expressed by monocytes, endothelial cells, and smooth muscle cells. The study aimed to investigate MCP‑1’s role in atherogenesis by assessing its expression in human arteries. The authors performed in situ hybridization on 10 normal and 14 diseased human arteries to detect MCP‑1 mRNA. MCP‑1 mRNA was found in 16 % of cells in carotid endarterectomy specimens, predominantly in organizing thrombi (33 %) and macrophage‑rich regions (24 %), expressed by vascular smooth muscle cells, mesenchymal intimal cells, and macrophages, whereas it was almost absent in normal arteries (<0.1 %), indicating a potential role in monocyte infiltration of the arterial wall.

Abstract

Monocytes appear to be central to atherogenesis both as the progenitors of foam cells and as a potential source of growth factors mediating intimal hyperplasia, but the chemical messages which stimulate the influx of monocytes into human atheroma remain unknown. Monocyte chemoattractant protein-1 (MCP-1) is a recently described molecule with powerful monocyte chemotactic activity expressed by monocytes, vascular endothelial cells, and smooth muscle cells in culture. To begin to address the role of MCP-1 in vivo, we examined 10 normal arteries and 14 diseased human arteries for MCP-1 expression by in situ hybridization. MCP-1 mRNA was detected in 16% of 10,768 cells counted in human carotid endarterectomy specimens with highest expression seen in organizing thrombi (33%) and in macrophage rich areas bordering the necrotic lipid core (24%) as compared to the fibrous cap (8%) and the necrotic lipid core itself (5%). Based on immunohistochemical staining of serial sections and on cell morphology, MCP-1 mRNA appeared to be expressed by vascular smooth muscle cells (VSMC), mesenchymal appearing intimal cells (MICs), and macrophages. By contrast, few cells expressing MCP-1 mRNA were found in normal arteries (less than 0.1%). These data suggest a potential role for MCP-1 in mediating monocytic infiltration of the artery wall.