Cigarette smoke exposure promotes arterial thrombosis and vessel remodeling after vascular injury in apolipoprotein E-deficient mice.
BACKGROUND
Cigarette smoking is a major risk factor for the development of cardiovascular disease. However, in terms of the vessel wall, the underlying pathomechanisms of cigarette smoking are incompletely understood, partly due to a lack of adequate in vivo models.


METHODS
Apolipoprotein E-deficient mice were exposed to filtered air (sham) or to cigarette mainstream smoke at a total particulate matter (TPM) concentration of 600 microg/l for 1, 2, 3, or 4 h, for 5 days/week. After exposure for 10 +/- 1 weeks, arterial thrombosis and neointima formation at the carotid artery were induced using 10% ferric chloride.


RESULTS
Mice exposed to mainstream smoke exhibited shortened time to thrombotic occlusion (p < 0.01) and lower vascular patency rates (p < 0.001). Morphometric and immunohistochemical analysis of neointimal lesions demonstrated that mainstream smoke exposure increased the amount of alpha-actin-positive smooth muscle cells (p < 0.05) and dose-dependently increased the intima-to-media ratio (p < 0.05). Additional analysis of smooth muscle cells in vitro suggested that 10 microg TPM/ml increased cell proliferation without affecting viability or apoptosis, whereas higher concentrations (100 and 500 microg TPM/ml) appeared to be cytotoxic.


CONCLUSIONS
Taken together, these findings suggest that cigarette smoking promotes arterial thrombosis and modulates the size and composition of neointimal lesions after arterial injury in apolipoprotein E-deficient mice.
Schroeter
Marco R
MR
Department of Cardiology and Pulmonary Medicine, Georg August University of Göttingen, Göttingen, Germany.
Sawalich
Matthias
M
Humboldt
Tim
T
Leifheit
Maren
M
Meurrens
Kris
K
Berges
An
A
Xu
Haiyan
H
Lebrun
Stefan
S
Wallerath
Thomas
T
Konstantinides
Stavros
S
Schleef
Raymond
R
Schaefer
Katrin
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014654:Vascular Patency / Q000187:drug effects
D000199:Actins; D001057:Apolipoproteins E; D002712:Chlorides; D005290:Ferric Compounds; D012906:Smoke; C024555:ferric chloride