Progression of atherosclerosis in the Apo E-/- model: 12-month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet.
This study was performed to gain information about the influence of two cardiovascular risk factors, cigarette mainstream smoke (MS) and high-cholesterol/fat diet, on the progression of atherosclerosis in apolipoprotein E-deficient (Apo E-/-) mice. Eight to 12-week-old mice were whole-body exposed for up to 12 months (6h/day, 5 days/week) to diluted cigarette mainstream smoke at total particulate matter (TPM) concentrations of 100 or 200mg/m(3), or to filtered fresh air (sham) in combination with a normal chow diet or a high-cholesterol/fat diet. Cholesterol in the aortic arch was elevated in the high-cholesterol/fat diet groups exposed to 200 mg TPM/m(3) compared to sham at all time points. In the brachiocephalic artery (BA), absolute plaque size and fraction area of plaques was elevated over the 12-month time course in mice exposed to 200 mg TPM/m(3) compared to sham (both diets). Exposure to 100 and 200 mg TPM/m(3) altered the number of elastin-rich layers in the BA in mice fed a high-cholesterol/fat diet, indicating changes in plaque morphology at 6 and 9 months. This study shows for the first time the influence of two different risk factors, MS and high-cholesterol/fat diet, both alone and in combination over a period of 12 months, on the progression of atherosclerosis in Apo E-/- mice. Data suggest that long-term exposure to cigarette mainstream smoke accelerates the development of atherosclerosis in Apo E-/- mice, particularly in combination with a high-cholesterol/fat diet.
von Holt
K
K
PHILIP MORRIS Research Laboratories GmbH, Cologne, Germany. Klaus@vonholt.de
Lebrun
S
S
Stinn
W
W
Conroy
L
L
Wallerath
T
T
Schleef
R
R
D000821:Animal Feed; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics*; D016122:Brachiocephalic Trunk / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052638:Particulate Matter; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
D001057:Apolipoproteins E; D004041:Dietary Fats; D052638:Particulate Matter; D012906:Smoke; D002784:Cholesterol