title: The heart as an extravascular target of endothelin-1 in particulate matter-induced cardiac dysfunction.
abstract: Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease have been explored, although linkage with specific factors or genes remains limited. These hypotheses may or may not also lead to particulate matter-induced cardiac dysfunction. Evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction has increased interest in the emerging role of endothelins as mediators of cardiac function following particulate matter exposure. Endothelin-1, a well-described small peptide expressed in the pulmonary and cardiovascular systems, is best known for its ability to constrict blood vessels, although it can also induce extravascular effects. Research on the role of endothelins in the context of air pollution has largely focused on vascular effects, with limited investigation of responses resulting from the direct effects of endothelins on cardiac tissue. This represents a significant knowledge gap in air pollution health effects research, given the abundance of endothelin receptors found on cardiac tissue and the ability of endothelin-1 to modulate cardiac contractility, heart rate, and rhythm. The plausibility of endothelin-1 as a mediator of particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. The present review examines the possibility that endothelin-1 release caused by exposure to PM directly modulates extravascular effects on the heart, deleteriously altering cardiac function.
authors.affiliation: Oak Ridge Institute for Science and Education (ORISE) Fellow at the National Center for Environmental Assessment, U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC, USA.
authors.forename: Elizabeth A W
authors.initials: EA
authors.lastname: Chan
authors.affiliation: National Center for Environmental Assessment, U.S. EPA, Research Triangle Park, NC, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Buckley
authors.affiliation: Environmental Public Health Division, U.S. EPA, Research Triangle Park, NC, USA.
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.affiliation: Environmental Public Health Division, U.S. EPA, Research Triangle Park, NC, USA. Electronic address: thompson.leslie@epa.gov.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D066126:Cardiotoxicity; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004781:Environmental Exposure / Q000009:adverse effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D052638:Particulate Matter / Q000009:adverse effects*; D015398:Signal Transduction
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D052638:Particulate Matter
keywords: Air pollution; Autocrine/paracrine signaling; Cardiac dysfunction; Endothelin-1; Heart; Particulate matter