TYPE-I COLLAGEN GENE-EXPRESSION IN HUMAN ATHEROSCLEROSIS - LOCALIZATION TO SPECIFIC PLAQUE REGIONS

Because collagen is a major component of the human atherosclerotic pla que, factors controlling collagen synthesis may have a profound influe nce on the volume growth of these intimal lesions. In human arteries, we compared normal vs atherosclerotic medias vs intimas for type I col lagen gene expression using immunocytochemistry and in situ messenger RNA hybridization with subsequent correlations with plaque topographic al features. We also determined the associations of such collagen gene expression with proximity to monocyte/macrophages and T lymphocytes. Type I collagen synthesis appears to be upregulated in atherosclerotic plaques compared with their underlying medias and normal internal mam mary arteries and coronary diffuse intimal thickenings. At least in es tablished and advanced coronary and carotid plaques, type I collagen g ene expression is focal and especially prevalent in fibrous cap and va scularized regions. Although macrophages and type I procollagen messen ger RNA and protein are both found in atherosclerotic plaques, no appa rent spatial correlation between macrophage presence and type I procol lagen presence was found within these atherosclerotic intimas. Type I procollagen presence appears to be negatively associated with the spat ial presence of T cells. Thus, human atherosclerotic plaques exhibit n onuniform patterns of type I collagen gene expression. Although the bi ochemical determinants of this focal gene expression have yet to be de termined, it is conceivable that stimulatory/inhibitory cytokines and other factors (eg hemodynamics) play important roles in determining th e focal nature of collagen synthesis in atherosclerosis.