EXPRESSION OF BASIC AND ACIDIC FIBROBLAST GROWTH-FACTORS AND THEIR RECEPTOR IN NORMAL AND ATHEROSCLEROTIC HUMAN ARTERIES

Objective: Acidic and basic fibroblast growth factors (FGF) are potent mitogens for vascular endothelial and smooth muscle cells and also promote angiogenesis. Given that atheroma is associated with the proliferation of a range of cell types, including smooth muscle cells, it has been proposed that these growth factors may play a part in the genesis and/or maintenance of atheromatous lesions. The aim of our study was to examine the distribution of acidic and basic FGF and their known receptor, fibroblast growth factor receptor 1 (FGFR-1), in normal and atherosclerotic arteries. Methods: Formalin fixed wax embedded archival material from a wide range of vessels was examined using a three stage avidin-biotin immunoperoxidase technique and specific polyclonal antibodies to acidic and basic FGF and FGFR-1. Results: In normal arteries basic FGF immunoreactivity was found in medial smooth muscle cells and adventitial blood vessels, the luminal endothelium being non-reactive. Acidic FGF expression was observed predominantly in adventitial fibroblasts, while FGFR-1 expression was confined to the adventitial microvasculature. In early, simple, and advanced lesions acidic and basic FGF were expressed in macrophages and smooth muscle cells, the principal cell types involved in atherosclerotic lesion formation. Increased expression of basic FGF and FGFR-1 was particularly associated with neovascularisation of the atheromatous lesions. Conclusions: Acidic and basic FGF are expressed in early, simple and advanced atherosclerotic plaques. This suggests that in vivo these growth factors may have a role in the genesis of this disease. Basic FGF and FGFR-1 may potentially be involved in plaque neovascularisation. Such FGF driven angiogenic events may be central to the life threatening complications of atheroma and provide new options for therapeutic intervention.