The Relationship Between Serum Mitochondrial Coupling Factor6, PGI₂and NO In Healthy Smokers

Background and Aim: There is a significant increase in morbidity and mortalityof cardiovascular disease in smokers recent years. Substantial evidence shows thatsmoking can cause diastolic dysfunction of endothelium-dependent vascular andmicrovascular. Endothelial dysfunction is considered a precursor of atherosclerosisinitiation, and atherosclerosis is the pathological basis of acute coronary syndrome.Prostaglandin I2（PGI₂）, as an endothelium-derived dilator, plays an important role incardiovascular regulating potentially. Previous studies have shown that inflammatoryfactor correlated cigarette smog can reduce the production of PGI₂. So it may be one ofthe important factors in the occurrence of cardiovascular disease that the serum PGI₂level is abnormal in smokers. In addition, mitochondrial coupling factor6（couplingfactor6, CF6）, the only endogenous PGI₂synthesis inhibitor is secreted by endothelium,which is the major resource from blood. It is well known that CF6can contract vessel,increase blood pressure and heart rate via circulating hormone-like model. It is thoughtthat smoking promotes release of CF6as it causes endothelial injury, which can alsocause diastolic dysfunction of endothelium-dependent vessels. However, vascularcontraction spasm and the change of blood shear stress can promote the release of CF6from endothelium. NO, mainly from endothelial cells, contains many biological effectsincluding inhibition of platelet aggregation and smooth muscle cell proliferation,regulate vascular tone, mediate cellular immunity and cytotoxic effect. And it is one ofthe markers of endothelial injury and is of great significance in cardiovascular disease.However, changes of CF6in smokers, whether there is some relationship between PGI₂change and CF6in smokers are still unclear. And the relationship between CF6changeand endothelial dysfunction and its pathophysiological significance are also not clear. Inthis study, we investigated any relationship between the serum levels of CF6, PGI₂and NOamong healthy smokers and non-smokers, thus learn more about the hazards ofsmoking on vascular endothelium, providing a new clinical evidence for coronary heartdisease caused by smoking.Methods:90volunteers were enrolled in this study including59healthy smokersand31healthy non-smokers. The healthy smokers were divided into light and heavysmokers. The three groups （lightsmoker, heavy smoker and non-smoker） were defineddepending on cigarette index （CI）.[CI<200, CI≥200and CI=0respectively]. The serumlevels of mitochondrial CF6and PGI₂were tested withEnzyme-Linked ImmunosorbentAssay （ELISA）, while the serum level of NO was determined by nitrate reductasemethod. The serum levels of total cholesterol （TC）, triglycerides （TG）, low densitylipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C） andfasting blood glucose （FBG） were also detected conventionally. All datas wereprocessed by SPSS17.0, and there was a statistical significance if the value of P<0.05.Results:1. The serum levels of mitochondrial CF6in CI≥200group（208.85±14.18ng/L） were higher than those in CI=0（163.81±14.83ng/L） and CI<200（188.53±9.29ng/L） groups, while CF6levels in CI<200group were also higher thanthose in CI=0group. There was a statistical differenceamong three groups （P<0.05）.2.The serum concentrations of PGI₂in group which CI≥200（79.978±5.532ng/L） werelower than CI=0（105.086±6.186ng/L） group and CI<200group （90.112±4.839ng/L）,and PGI₂levels in CI≥200group were lower than those in CI=0group. Statisticalsignificance existed among all three groups.3. The serum concentrations of NO testedbetween CI=0, CI<200and groups were100.19±4.10μmol/L,88.94±4.16μmol/L andwere higher than those in CI≥200group （80.61±6.87μmol/L）. On comparison betweenthese groups there was statistical significance （P<0.05）.4. Mitochondrial CF6had asignificantly negative correlation with serum levels of PGI₂and NO（r=-0.418, P<0.05;r=-0.326, P<0.05）. But a significantly positive correlation was found between the serumlevels of PGI₂and NO （r=0.323, P<0.05）.5. The correlation analysis of CF6showedthat CF6was independently associated with CI （β=2.331, P=0.022） and PGI₂（β=-0.320,P=0.003）. The levels of CF6increased with the enhancement of CI.6. According to thePGI₂’s correlation analysis, it showed that CI （β=-0.422, P<0.01） and CF6（β=-0.320,P=0.002） were independently correlated with PGI₂.In addition, PGI₂decreased with theincreases of CI and CF6.7. The correlation analysis of NO showed that NO wasindependently associated with CI （β=-0.156, P=0.037） and NO decreased with the increase of CI.Conclusion:1. This study clearly shows that smoking can lead to an increase inserum level of CF6and a decrease inthe serum level of NO and PGI₂. These levels areindependently associated with CI. All above show that smoking can cause endothelialinjury. CF6is a marker of vascular endothelial injury induced by smoking, while also apathogenic factor of that process.2. Moreover in this study, a significantly independentcorrelationwas found between the increase of CF6and the decease of PGI₂, showingthat serum level of CF6plays a role in the decrease of serum PGI₂.