N. Abdalla,1 M. Parvez,1 Y. Yu,1 M. Yi,1 H. Shin,1 D. Kim,1 D. Kim,1 J. Shin2; 1Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea, Republic of, 2Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine; Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea, Republic of
BACKGROUND: Cigarette smoking is strongly associated with a large number of cardiovascular diseases. In addition, eicosanoid pathway is of significant importance in cardiovascular disease (CVD) due to its role in maintaining vascular wall tone, regulating coagulation, and platelet activation pathways. We hypothesized that certain metabolites of this pathway which have been linked with CVD could be altered due to chronic cigarette smoking.
METHODS: In the current study, we observed the concentration changes as well as inter-metabolite correlations in plasma and urine arachidonic acid metabolites in male smokers and non-smokers.
The metabolites were extracted using solid phase extraction techniques and quantified using LC-MS/MS methods. Multivariate correlation analysis was done to identify the pattern of correlation between metabolites, and the association between the metabolites and other clinical parameters was done using regression analysis.
RESULTS: Significant differences in plasma and urine metabolites were observed between smokers and non-smokers. In the case of plasma, higher concentration levels were observed in 11-HETE, 20-HETE, 11,12-DHET, and 14,15-DHET (P<0.05). While in the urine, higher concentrations of 11-dhTXB2 were observed (P<.0.01). Smokers also showed strong inter-metabolite correlations between 20-HETE and the DHET isomers. In addition, age and blood pressure were significantly associated with urine and plasma metabolites, mainly the HETEs and thromboxane metabolites (P<0.05).
CONCLUSION: The elevated levels of plasma 20-HETE and DHETs isomers in smokers may play an important role in the pathophysiological mechanisms associated with the cardiovascular disease.