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Cigarette smoke‐induced pro‐inflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation
Author(s) -
Orosz Zsuzsanna,
Csiszar Anna,
Labinskyy Nazar,
Smith Kira,
Rivera Aracelie,
Kaminski Pawel,
Ferdinandy Peter,
Wolin Michael S.,
Ungvari Zoltan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a450-b
Subject(s) - apocynin , nad(p)h oxidase , nadph oxidase , nad+ kinase , oxidative stress , oxidase test , inflammation , catalase , chemistry , reactive oxygen species , pharmacology , in vivo , medicine , endothelial dysfunction , biochemistry , enzyme , biology , microbiology and biotechnology
Although the cardiovascular morbidity and mortality induced by cigarette smoking exceeds that attributable to lung cancer, the molecular basis of smoking‐induced vascular injury remains unclear. To test the link between cigarette smoke, oxidative stress and vascular inflammation, rats were exposed to the smoke of 5 cigarettes per day (for one week). Also, isolated arteries were exposed to cigarette smoke extract (CSE; 0 to 40 ug/mL, for 6 h) in organoid culture. We found that smoking impaired acetylcholine‐induced relaxations of carotid arteries, which could be improved by the NAD(P)H oxidase inhibitor apocynin. Both smoking and in vitro CSE exposure significantly increased vascular O2.‐ and H2O2 production. Vascular mRNA expression of the pro‐inflammatory cytokines IL‐1beta, IL‐6 and TNFalfa and that of iNOS was significantly increased by both smoking and CSE exposure, which could be prevented by inhibition of NAD(P)H oxidase (DPI, apocynin) or scavenging of H2O2. In cultured endothelial cells CSE elicited NF‐kB activation and increased monocyte adhesiveness, which were prevented by apocynin and catalase. Thus, we propose that water soluble components of cigarette smoke (that are likely to be present in the bloodstream in vivo in smokers) activate the vascular NAD(P)H oxidase. NAD(P)H oxidase‐derived H2O2 activates NF‐kB leading to pro‐inflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis, especially if other risk factors are also present. (Grant support: NIH HL077256, Philip Morris USA).