International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/1. Mutational events in the etiology of arteriosclerotic plaques.
The arteriosclerotic plaque is the lesion most often associated with cardiovascular disease, which is the leading cause of death in North America and Western Europe. Plaques are composed of cells (mostly smooth muscle cells but also macrophages and some lymphocytes) and formed elements (cellular debris, collagen, elastin, glycosaminoglycans, lipid droplets, cholesterol crystals and sometimes calcium deposits). Proliferation of smooth muscle cells is essential to plaque formation and development. Most theories of plaque development have viewed this proliferation as a secondary event following an initiating stimulus (e.g., endothelial injury). According to this view, the proliferating smooth muscle cells are otherwise identical to the large number of non-proliferating smooth muscle cells in the artery wall. The 'monoclonal' hypothesis of plaque formation presents a fundamentally different view; namely, that the cell proliferation critical to plaque development follows the stable transformation of smooth muscle cells and that the plaques can therefore be viewed as benign smooth muscle cell tumors of the artery wall. Environmental agents, including viruses and chemicals that have been previously associated with cell transformation and tumorigenesis may therefore also contribute directly to plaque development. Data are provided from in vivo and in vitro studies in support of this proposition. Evidence is also presented that in standardized assays human and animal plaque DNAs elicit responses similar to those elicited by tumor DNAs. Thus, both plaque formation and tumorigenesis may share common mechanisms.
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Institute of Environmental Medicine, New York University, NY 10016.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects; D000818:Animals; D001151:Arsenic / Q000009:adverse effects; D001161:Arteriosclerosis / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000009:adverse effects; D004249:DNA Damage; D006564:Herpesviridae / Q000472:pathogenicity; D006801:Humans; D008748:Methylcholanthrene / Q000009:adverse effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009154:Mutation; D014170:Transformation, Genetic
D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D001151:Arsenic