Smoking increases inflammation and metalloproteinase expression in human carotid atherosclerotic plaques

Simon Kangavari, Shlomo Matetzky, Prediman K. Shah, Juliana Yano, Kuang Yuh Chyu, Michael C. Fishbein, Bojan Cercek*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objectives: 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.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Issue number4
StatePublished - Dec 2004
Externally publishedYes


  • Atherosclerosis
  • Endarterectomy plaques
  • Inflammation
  • Smoking


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