Synthesis of TNFα and TGFβ mRNA in the different micro-environments within atheromatous plaques.

Objective: To examine localisation of tumour necrosis factor (TNFα) and transforming growth factor β (TGFβ) mRNA synthesis in human coronary artery atheromatous plaques, to explore how synthesis of these cytokines relates to distribution of macrophages and smooth muscle cells, and to correlate this with plaque micro-environments. Method: In situ hybridisation with digoxigenin-labelled sense and anti-sense riboprobes was used, combined with immunohistochemistry to detect TNFα protein, macrophage, lymphocyte and smooth muscle cell markers. Results: In the intimal plaque TNFα mRNA is synthesised by monocytes/macrophages as well as by smooth muscle cells. Both TNFα and TGFβ mRNAs were present at the margins of the lesions and in reactive areas, where there was little lipid and fibrosis. Focal aggregates of macrophages in the adventitia expressed both TNFα mRNA and protein and TGFβ mRNA. Conclusion: Synthesis of these two cytokines by macrophages as well as smooth muscle cells contributes to the pathobiology of the plaque and that this is part of the ‘reaction to injury’, rather than a feature of a specific cell, or a specific layer, within the vessel wall. [ABSTRACT FROM PUBLISHER]