Responses of vascular smooth muscle cells to toxic insult: Cellular and molecular perspectives for environmental toxicants

Kenneth S. Ramos, Russell C. Bowes, Xiaolan Ou, Thomas J. Weber

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Over the past several decades emphasis has been given to the elucidation of mechanisms involved in the onset and progression of cardiovascular disorders. Stroke, hypertension, and atherosclerosis continue to rank as primary causes of death in the western world. In the case of atherosclerosis, the preferential localization of atheroma to largeand mediumsized blood vessels and the sequence of events leading to plaque development have been well defined. Damage to luminal endothelial and/or medial smooth muscle cells, migration of inflammatory cells, diffusion or local delivery of mediators within the vessel wall, proliferation of vascular smooth muscle cells, and cellular accumulation of lipids are now recognized as hallmarks of the pathologic process. Although these events have been established with a fair degree of certainty, the mechanisms responsible for initiation of the atherosclerotic process are not yet completely understood. Environmental chemicals have come under increasing scrutiny as evidence continues to accumulate suggesting that toxic insult plays an important role in the initiation and/or progression of atherosclerotic disorders. This review focuses on various aspects of xenobiotic-induced vascular injury with emphasis on the toxic effects of allylamine and benzofalpyrene in smooth muscle cells, the primary cellular component of atherosclerotic lesions. Both of these chemicals modulate growth and differentiation programs in aortic smooth muscle cells and have been implicated in the development of atherosclerotic-like lesions in laboratory animals. The major findings from recent studies examining the cellular and molecular basis of toxicant-induced phenotypic modulation of vascular smooth muscle cells to a proliferative state and the role of oxidative metabolism, phospholipid turnover, protein kinase C, ras-related signal transduction, and matrix interactions in the vasculotoxic response to allylamine and benzolajpyrene are discussed.

Original languageEnglish (US)
Pages (from-to)419-440
Number of pages22
JournalJournal of Toxicology and Environmental Health
Volume43
Issue number4
DOIs
StatePublished - Dec 1994
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pollution

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