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Cigarette smoking is a major cause of mortality and morbidity worldwide.  Cyclooxygenase (COX and its derived prostanoids, mainly including prostaglandin E2 (PGE2), thromboxane A₂ (TXA₂) and prostacyclin (PGI2), have well-known roles in cardiovascular disease and cancer, both of which are associated with cigarette smoking.  This article is focused on the role of the COX-2 pathway in smoke-related pathologies and cancer."

"Cigarette smoke exposure can induce COX-2 expression and activity, increase PGE2 and TxA₂ release, and lead to an imbalance in PGI2 and TxA₂ production in favor of the latter."

"Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention.  We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease."

“Measurement of TXB₂ levels in human plasma would be indicative of circulating levels in the blood. Thromboxane B₂ levels were found to be significantly (p<0.01) higher in plasma samples taken from patients with NSCLC, relative to age-matched controls (3307 ± 189 pg/mL versus 2201 ± 317 pg/mL); n= 49 NSCLC patients, 19 cancer-free controls."

"Diabetic patients commonly present an increased risk for cardiovascular events, for which aspirin is the most frequently used medication for primary prevention.  Urinary 11-dehydro thromboxane (11-dhTXB₂) concentrations assess the effect of aspirin on platelets and identify patients who are at risk of cardiovascular events.  The present study investigated whether or not type 2 diabetic patients who took a daily dose of 100 mg of aspirin had a signficant reduction in urinary 11-dhTXB₂ concentrations and whether these results were associated with clinical and laboratory variables."

“Most patients enrolled in the present study also presented a reduced or minimal response to low-dose aspirin therapy, thereby indicating a clear variability related to aspirin effectiveness."

"This article describes the data mining analysis of a clinical exposure study of 3,585 adult smokers and 1077 nonsmokers.  The analysis focused on developing models for four biomarkers of potential harm:  white blood cell count (WBC), 24 h urine 8-ep-prostaglandin F2a, (EP18), 24 h urine 11-dehydro-thromboxane B2 (DEH11),  and high-density lipoprotein cholesterol (HDL)."

"Levels of WBC, EPI8, DEH11 and HDL were statistically associated with biomarkers of exposure to cigarette smoking and demographics and lifestyle factors."

"Metabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes.  Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low-grade inflammation, alterred oxidative/antioxidant status, and persistent platelet activation."

"We examined the effects of short-term vitamin E supplementation (600 mg daily for 2 week) on the urinary excretion of 8-iso-PGF2alpha and 11-dehydro-TXB_2. Vitamin E supplementation was associated with detectable changes in plasma vitamin E levels and caused virtually complete normalization of 8-iso-PGF2alpha excretion. Moreover, changes in F2-isoprostane formation were accompanied by similar reductions in thromboxane metabolite excretion."

"It is well admitted that the link between chronic inflammation and cancer ionvolves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis.  The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis.  This family contains three members:  ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated."

"Atherosclerosis and its clinical manifestations (i.e. myocardial infarction, stroke) are major causes of mortality and morbidity in Western countries.  Atherogenesis is a pathological process characterised by the deposition of lipids and other blood-borne materials in the arterial wall.  Endothelial dysfunction is considered the first step in the cascade leading up to coronary events."

“Dysfunctional endothelium, characterized by increased COX-activity, releases prostanoids that promote endothelial exposure to adhesion molecules and induce smooth muscle cell contraction.”

"Several clinical and In Vitro studies showed that polyphenols are able to inhibit platelet activation, preventing cerebro- and cardiovascular disease.  The Mediterranean diet includes fruit and vegetables rich in polyphenols known as effective protective agents.  Fruits and vegetables contain polyphenols such as tannins found in red wine and phenolic acid, flavonones, anthoscyanin, flavonols, stilbenes, and lignans found in pomegranates as protective agents from the hot Meditarranean sunshine."

“We have shown that pomegranate juice reduces every step of platelet activation, such as platelet aggregation, calcium mobilization, hydrogen peroxide formation, and TxA₂ production induced by collagen and arachidonic acid.”

“Epidemiological studies indicate that the consumption of red wine reduces the mortality and morbidity from CAD. Muscadine grapes contain high levels of antioxidants, including resveratrol, a polyphenol with multiple cardioprotective effects.” 

"These antioxidants are thought to be the effective agents behind the so-called "French Paradox," the low mortality rate from CAD amongs the French population desipite their high-fat diet and smoking."

"Resveratrol has been shown to inhibit lipid peroxidation of LDL, prevent the cytoxicity of oxidized LDL, protect cells against lipid peroxidation, reduce platelet aggregation, and inhibit vascular SMC proliferation".

"Significant statistical differences between smokers with approximately 10 years of smoking history and non-smokers in white cell count, hemoglobin and thromboxane turnover were seen, although they did not reach levels associated with overt diseases."