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Bi‐modal Dose‐Response Relationship Between Ambient Ultrafine Particulate Matter (UFP) Exposure and Cardiovascular End‐Points in Mice
Author(s) -
Lust Robert M,
Cozzi Emily,
Henriksen Ruth Ann,
Wingard Christopher J,
Cascio Wayne E,
Devlin Robert B,
Van Scott Michael R
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a811-c
Epidemiological studies link the level of particulate matter in air and adverse cardiovascular events; animal models have revealed direct exposure to ultrafine particulate matter (UFP) alters vascular reactivity, severity of myocardial ischemia/reperfusion (I/R) injury, and thrombogenic potential. We investigated the dose dependent effects of UFP on I/R injury, blood cell counts, and hemostasis. Mice were exposed to saline vehicle and UFP (10, 30, and 100 μg doses) by intratracheal instillation. Blood samples were collected for differential cell counts, analysis of fibrinogen levels, and aortas were isolated to evaluate vascular reactivity. In other animals, I/R injury was induced. I/R injury exhibited a bi‐modal dose‐response relationship: 10 and 100 μg doses of UFP increased the size of the induced injury, but 30 μg had no effect. An inverse relationship was observed in total blood leukocyte counts 10 and 100 μg UFP decreased counts, 30 μg had no effect. The 100 μg dose increased the number of platelets in blood and reduced vascular relaxation to Ach. UFP induces different cardiovascular effects through discrete mechanisms, and a constellation of the effects may be necessary to precipitate debilitating cardiovascular crisis at high levels of exposure. This abstract of a proposed presentation does not necessarily reflect EPA policy. Funding support in part by Phillip Morris US and International.