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Chapter 12

Metals in Environmental Cardiovascular Diseases

Metals are essential to cardiovascular function and health, but their toxicities are among the oldest known. Their role in promoting cardiovascular diseases and their mechanisms for affects in heart and vascular tissues are often unrealized or controversial. Exposure to metals is widespread and may produce greater effects in susceptible populations or when exposures occur during development. There is increased appreciation that environmental exposures to metals or exposures even at occupational or therapeutic levels may have more subtle effects in causing or modifying disease. Uncertainty in understanding mechanisms of metal action often comes from the approach of using high dose toxicity studies that determine acute toxicities non-human mammals to identify pathogenic etiology in humans who often experience much lower chronic exposures. Mechanisms of metals or metalloid action are often thought to be caused by disrupting the normal signaling of selective ion channels, mediated by random interactions with peptide or protein sulfhydryls, or similarly produced by random oxidant injury. While this may be true for the highest levels of exposure, recent epidemiological studies and studies in genetic rodent models indicate that pathogenic effects of metals on cell signaling are not random. Not all of the effects are accounted for by direct competition with endogenous ions or oxidant-mediated processes. Resolving the molecular understanding of these pathogenic effects and toxicities is complicated by complex differential concentration- and time-dependent actions of metals in different cell types, as well as a high degree of interactions between metals in common mixed exposures. This chapter presents toxic effects of metals in the heart and blood vessels with an emphasis on the cellular and molecular actions underlying disease and clinically significant toxicities that are directly linked to human exposures to metals.

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03 Dec 2010
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From the book series:
Issues in Toxicology