Modification of Smoke Toxicant Yields Alters the Effects of Cigarette Smoke Extracts on Endothelial Migration

Abstract

Endothelial damage plays a key role in atherosclerosis and this is impacted upon by numerous risk factors including cigarette smoking. A potential measure to reduce the cardiovascular burden associated with smoking is to reduce smoke toxicant exposure. In an in vitro endothelial damage repair assay, endothelial cell migration was inhibited by cigarette smoke particulate matter (PM) generated from several cigarette types. This inhibition was reduced when cells were exposed to PM from an experimental cigarette with reduced smoke toxicant levels. As a number of toxicants induce oxidative stress and since oxidative stress may link cigarette smoke and endothelial damage, we hypothesized that PM effects were dependent on elevated cellular oxidants. However, although PM-induced cellular oxidant production could be inhibited by ascorbic acid or n-acetylcysteine, both these antioxidants were without effect on migration responses to PM. Furthermore, reactive oxygen species production, as indicated by dihydroethidium fluorescence, was not different in cells exposed to smoke from cigarettes with different toxicant levels. In summary, our data demonstrate that a cardiovascular disease-related biological response may be modified when cells are exposed to smoke containing different levels of toxicants. This appeared independent of the induction of oxidative stress.

Examination of the use of human sera as an exposure agent for in vitro studies investigating the effects of cigarette smoking on cellular cardiovascular disease models

“…A healthy endothelium possesses an innate repair capability that ensures that damage to the endothelial lining is repaired effectively, restoring blood vessel homeostasis and preventing disease progression (Bai et al, 2010). In smokers, repair processes such as endothelial migration are impaired and this can lead to further events that contribute to disease progression (Fearon et al, 2012). Using a scratch wound model of endothelial damage repair, we have previously shown that exposure to cigarette smoke particulate matter inhibits endothelial migration in vitro (Fearon et al, 2012).…”

“…Together, these reports propose that data from disease-relevant in vitro models are useful in the assessment of the biological effects of reducedtoxicant cigarettes and may contribute to product evaluation (Stratton et al, 2001; Committee on Scientific Standards for Studies on Modified Risk Tobacco Products, Institute of Medicine, 2012). To this end, we have recently demonstrated that an in vitro CVD-related biological response was modified when endothelial cells were exposed to smoke extracts from cigarettes that contained different levels of toxicants (Fearon et al, 2012).…”

Absence of Smoker’s Paradox in Middle Eastern Patients with Acute Coronary Syndrome

“…Cigarette smoking adversely affects the cardiovascular system through several mechanisms: arterial endothelium injury, low-grade inflammation, increase in plasma fibrinogen, enhanced platelet aggregation, catecholamine release and increase in heart rate and arterial blood pressure, vasoconstriction, and reduction in myocardial oxygen delivery [4][5][6][7][20][21][22]. "Smoker's paradox" describes the observations that smokers experience decreased mortality when they sustain NSTEACS or STEMI, or when they undergo percutaneous coronary intervention (PCI) compared with non-smokers.…”

“…It is known for its role in impairing endogenous fibrinolysis, enhancing platelet aggregation and thrombus formation, and promoting the development of a thin fibrous cap in atherosclerotic coronary plaques, thus predisposing the plaque to erosion and subsequent thrombosis leading to acute coronary syndrome (ACS) [4][5][6][7]. However, various studies have shown that smokers have lower mortality rates following ACS than non-smokers, suggesting that smoking has a protective effect in ACS giving rise to the concept of the "smoker's paradox", in which smokers are more likely to suffer ACS but also more likely to survive [8][9][10].…”

Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis

“…Differences in recent studies may be attributed to the combination of a particular VEGF-SNP with environmental risk factors, such as cigarette smoking (13). In addition, a higher risk for urothelial carcinoma in cigarette smokers harbouring the high-risk VEGF genotypes was previously described (14) and it was hypothesized that smoking may impair VEGF-induced cell migration (15). Chen et al (16) demonstrated that the -2578 AA genotype decreased disease activity in rheumatoid arthritis in non-smokers, but lost its protective properties in smokers.…”