Cardiac and vascular changes in mice after exposure to ultrafine particulate matter.
Increased ambient air particulate matter (PM) concentrations are associated with risk for myocardial infarction, stroke, and arrhythmia, and ultrafine PM (UFPM) might be particularly toxic to the cardiovascular system. Recent epidemiological studies are beginning to offer mechanistic insights, yet the rodent model remains a valuable tool to explore potential mechanisms. This article reviews a series of studies from our laboratory demonstrating the promise of mouse models to link health effects to biological mechanisms. Specifically, data from 6- to 10-wk-old male ICR mice exposed to intratracheal instillation of 100 microg of UFPM collected from the Chapel Hill, NC airshed are described. Studies of ischemia/reperfusion, vascular function, and hemostasis are described. In summary, UFPM exposure doubles the size of myocardial infarction attendant to an episode of ischemia and reperfusion while increasing postischemic oxidant stress. UFPM alters endothelial-dependent and -independent regulation of systemic vascular tone; increases platelet number, plasma fibrinogen, and soluble P-selectin levels; and reduces bleeding time, implying enhanced thrombogenic potential. Taking these findings together, this model of acute UFPM exposure in the mouse indicates that UFPM induces a prothrombotic state and decreases vasomotor responsiveness, thereby offering insight into how UFPM could contribute to vascular events associated with thrombosis and ischemia and increasing the extent of infarction.
Cascio
Wayne E
WE
Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA. casciow@ecu.edu
Cozzi
Emily
E
Hazarika
Surovi
S
Devlin
Robert B
RB
Henriksen
Ruth A
RA
Lust
Robert M
RM
Van Scott
Michael R
MR
Wingard
Christopher J
CJ
D000280:Administration, Inhalation; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008813:Mice, Inbred ICR; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000503:physiopathology; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage* / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D052638:Particulate Matter