Smoking increases inflammation and metalloproteinase expression in human carotid atherosclerotic plaques.
OBJECTIVE
To evaluate the effects of cigarette smoking on the composition of human carotid endarterectomy plaques.


BACKGROUND
Smoking has been recognized as a major risk factor in atherogenesis. It is believed that smoking contributes to the atherosclerotic process and plaque instability in part by increasing the adherence of macrophages to the vessel wall and inducing the release of proteolytic enzymes. However, data are lacking in humans.


METHODS
Carotid endarterectomy specimens of 21 smokers and 21 nonsmokers matched for age, gender, and symptoms were immunohistochemically stained with antibodies against CD68 (macrophages [MAC]), macrophage-derived metalloelastase (MMP-12), and tissue inhibitor of metalloproteinase 1 (TIMP-1). Sections were also evaluated for elastin content by van Gieson staining. The stained areas were planimetrically quantified as the percentage of immunopositive tissue area of the total tissue area.


RESULTS
Smoking was associated with increased macrophage immunoreactivity (9.1% +/-7.4% vs 3.4% +/- 2.9%; P = .003) as well as increased expression of MMP-12 (13.4% +/- 6.7% vs 5.5% +/- 3.5%; P = .0004). However, plaques from smokers had decreased TIMP-1 expression (7.7% +/- 5.7% vs 13.1% +/- 8.5%; P = .04) and decreased elastin content (26.9% +/- 14.5% vs 38.9% +/- 18.4%; P = .02).


CONCLUSIONS
This study demonstrates that cigarette smoking increases markers of inflammation and tissue destruction in atherosclerotic plaques. This change in plaque composition may at least in part explain the effect of smoking on the instability of human atherosclerotic plaques.
Kangavari
Simon
S
Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Matetzky
Shlomo
S
Shah
Prediman K
PK
Yano
Juliana
J
Chyu
Kuang-Yuh
KY
Fishbein
Michael C
MC
Cercek
Bojan
B
D000368:Aged; D001161:Arteriosclerosis / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology*; D016022:Case-Control Studies; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12