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European Journal of Heart Failure 2005 7(2):167-172; doi:10.1016/j.ejheart.2004.05.007
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© 2005 European Society of Cardiology

Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF2{alpha}

Roswitha Wolframa, Anthony Oguoghob,1, Barbara Palumboc and Helmut Sinzinger*,b,d

a Department of Angiology, Medical University of Vienna Vienna, Austria
b Department of Nuclear Medicine, Medical University of Vienna Vienna, Austria
c Institute of Nuclear Medicine, University of Perugia Perugia, Italy
d Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria

* Corresponding author. Wilhelm Auerswald Atherosclerosis Research Group (ASF), Nadlergasse 1, Vienna A-1090, Austria. Tel.: +43-1-4082633; fax: +43-1-4081366. E-mail address: helmut.sinzinger{at}univie.ac.at


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
The role of oxidation injury as an important factor in the pathophysiology of cardiomyopathy (CMP) has recently gained increasing interest. Semiquantitative analysis for isoprostane, 8-epi-prostaglandin F2{alpha} (8-epi-PGF2{alpha}), and oxidised low-density lipoprotein (ox-LDL) of coronary vascular tissue samples derived from CMP patients revealed an increased extent and intensity of uptake as compared to the respective controls. To evaluate oxidative stress in vivo, we examined plasma, serum, salivary, and urinary 8-epi-PGF2{alpha} in patients with dilated CMP (n=20) and ischemic CMP (n=20) with decreased left ventricular ejection fraction (LVEF). Patients with coronary heart disease (CHD) (n=20) and 20 healthy, age-matched, and sex-matched controls were investigated in parallel. 8-Epi-PGF2{alpha} levels were correlated with the functional severity of heart failure [New York Heart Association (NYHA) classification] and LVEF. 8-Epi-PGF2{alpha} levels were matched according to risk factors (smoking and hypercholesterolemia) and were significantly higher in patients with CMP as compared to healthy controls and patients with CHD in all investigated compartments. A positive correlation between NYHA stages and 8-epi-PGF2{alpha}, as well as a negative correlation to LVEF, could be demonstrated in a subgroup analysis.

These findings reflect the enhanced oxidation injury in patients with CMP and, to a lesser extent, in CHD as compared to healthy controls, thus highly indicating the relevance of oxidative stress for the pathogenesis and progression of cardiovascular disease.

Key Words: CCSC, Canadian Cardiovascular Society Classification • CHD, coronary heart disease • CMP, cardiomyopathy • HDL, high-density lipoprotein • LDL, low-density lipoprotein • LVEF, left ventricular ejection fraction • NYHA, New York Heart Association • 8-Epi-PGF2{alpha} 8-epi-prostaglandin F2{alpha}

Received January 16, 2004; Revised March 25, 2004; Accepted May 5, 2004


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Oxidation injury has been found to play a key role in the pathogenesis of various diseases [1–3], among them heart failure, particularly due to coronary heart disease (CHD) [3,4]. This concept has recently been underlined by a variety of animal models [5,6]. In patients suffering from cardiomyopathy (CMP), the isolation and subsequent semiquantitative analysis of the extent and intensity of positive staining for isoprostanes in the vascular intima and media revealed increased concentrations of 8-epi-prostaglandin F2{alpha} (8-epi-PGF2{alpha}), and significantly higher values in patients with CHD as compared to controls [7]. In a recent publication, Mallat et al. [8] were able to demonstrate elevated 8-epi-PGF2{alpha} in the pericardial fluid of patients with heart failure due to CHD. Isoprostanes, which are formed in vivo by a nonenzymatic process from arachidonic acid catalysed by free radicals, have been proven to be reliable biomarkers of oxidative stress in vivo [5,6,9–19]. In another investigation, increase of PGF2{alpha} type III as an index of lipid peroxidation could be identified in severe heart failure [20]. In our own study, we evaluated the values of 8-epi-PGF2{alpha} in various compartments. We were able to demonstrate significantly different 8-epi-PGF2{alpha} levels in healthy controls as compared to patients with CMP and CHD. Within these groups, the presence of risk factors was able to affect values found in plasma, serum, saliva, and urine. These findings strongly suggest the importance of isoprostane measurement as a new noninvasive parameter for the diagnosis of severity and the prediction of progression and treatment success in patients suffering from CHD and heart failure.


   2. Patients and methods
Top
 Notes
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1. Patients and controls
Twenty healthy volunteers, 20 patients with CHD [with stable angina, stage II according to the Canadian Cardiovascular Society Classification (CCSC)], 20 patients with dilative CMP, and 20 patients with ischemic CMP were included into this study. All patient characteristics are listed in Table 1. In all included persons, total cholesterol (CH), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), as well as plasma, serum, urinary, and salivary 8-epi-PGF2{alpha}, were measured. In patients with CHD, left ventricular ejection fraction (LVEF) was assessed by radionuclide ventriculography and lipid lowering, and any other medication was documented as well. In patients with dilative CMP and ischemic CMP, the New York Heart Association (NYHA) status was documented additionally. Medication was recorded in all patients (Table 2). Blood was drawn in the morning after an at least 12-h overnight fasting period for CH, TG, HDL, LDL, and 8-epi-PGF2{alpha}. A 24-h urinary sample was collected at the same time and, after assessing the total urinary volume, an aliquot was stored at –70 °C.


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  		Table 1 Patient characteristics and correlations between the investigated groups

 


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  		Table 2 Cardiac medications

 
2.2. Plasma 8-epi-PGF2{alpha}
Blood samples were anticoagulated with 2% EDTA and 1 mg/ml (final blood volume) acetylsalicylic acid (ASA). Centrifugation at 4 °C to obtain plasma was done at 1000xg for 10 min. Plasma was removed and stored at –70 °C for not longer than 2 weeks until determination by enzyme immunoassay. The interassay variability was 5.5±1.7% and the intraassay variability was 2.5±0.7%. Normal value was <20 pg/ml (n=11).

Artificial in vitro formation of 8-epi-PGF2{alpha}, which easily could occur due to auto-oxidation of arachidonic acid or other fatty acids, was excluded by immediate determination of some samples (showing no difference to the respective controls).

2.3. Serum 8-epi-PGF2{alpha}
Blood was drawn into glass vials. Vials were placed immediately into water bath at 37 °C for exactly 60 min. Serum was removed after centrifugation (4 °C, 1000xg, 10 min) and stored until determination (enzyme immunoassay) not longer than 2 weeks at –70 °C. The interassay variability was 3.8±1.0% and the intraassay variability was 1.9±0.7%. Normal value was 120–150 pg/ml (n=17).

2.4. Urinary 8-epi-PGF2{alpha}
Urine was collected over 24 h. Ten-milliliter aliquots were adjusted to pH 4.0 with formic acid and taken for extraction. The eluate was subjected to silicic acid chromatography and further eluted. This final elute was dried, recovered in buffer, and assayed after dilution by enzyme immunoassay. Cross-reactivity of the antibody with PGs was <2%. Values are given in picograms of 8-epi-PGF2{alpha} per milligram of creatinine. The interassay variability was 6.4±2.3% and the intraassay variability was 2.7±0.8%. Normal value was 150–250 pg/mg creatinine (n=14).

2.5. Collection of saliva
After rinsing the mouth with tap water, unstimulated whole saliva was collected into sterile tubes with the patient's head tipped forward and the nose pointing to the floor. Saliva specimens were stored frozen at –70 °C not longer then 2 months until analyzed.

2.6. Salivary 8-epi-PGF2{alpha}
Salivary concentrations of 8-epi-PGF2{alpha} were determined by enzyme immunoassay and expressed as picograms per milliliter of saliva. Immunoassay was performed using specific polyclonal antibodies without extraction.

2.7. Statistical analysis
Statistical analysis was performed using the SAS statistical software (SAS Institute, Cary, NC). Continuous variables were presented as the mean±S.D., and categorical variables as frequencies and percentages. To analyze differences between groups, comparisons were made using the chi-square test or Fisher exact test for categorical variables comparisons, and analysis of variance (ANOVA) for continuous variables. Post-hoc comparisons among groups were performed using a Scheffe test. Two continuous variables were analyzed using correlations. A difference of p<0.05 was considered significant.


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
Patients' baseline demographics are depicted in Table 1. Age, the prevalence of male gender, and current smoking status were comparable in all four groups. LVEF was not available for healthy controls, and showed a significant decrease between CHD as compared to dilative and ischemic CMP (50±7 vs. 23±7 and 25±8, p<0.001, respectively). There was no statistical difference between the two CMP groups. TC levels again were comparable between all groups. As for HDL cholesterol, the highest value was found, as expected, within the healthy control group at 55±10, with a significant difference as compared to the CHD and CMP groups (43±8, 45±8, and 43±8, p<0.001, respectively). Values within CHD and CMP groups were again comparable. LDL cholesterol levels showed a trend to increase with deteriorating disease; however, no statistical difference was observed. Interestingly, TG levels were very inhomogenously distributed and lowest in the ischemic CMP group.

3.1. 8-Epi-PGF2{alpha} analysis
We performed analysis for 8-epi-PGF2{alpha} levels by controlling for the use of statins and smoking status. The results are depicted in Tables 3 and 4. After controlling for smoking, a significant difference of 8-epi-PGF2{alpha} concentration was found in plasma, serum, and urine between healthy controls and all the investigated groups, showing a constant increase of 8-epi-PGF2{alpha} levels with progression of disease (see Table 3). As for salivary 8-epi-PGF2{alpha} levels, no difference was observed between controls (52±15) and patients with CHD (60±17), but a significant difference occurred between controls and patients with CHD as compared to patients with dilative and ischemic CMP (p<0.001, respectively) as well as between dilative and ischemic CMP (95±15 vs. 90±21, p=0.05).


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  		Table 3 8-Epi-PGF2{alpha} analysis controlling for smoking

 


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  		Table 4 8-Epi-PGF2{alpha} analysis controlling for smoking and statin use

 
Twelve patients with CHD (60%), 13 with ischemic CMP (65%), and 5 patients with dilative CMP (25%) received lipid-lowering therapy with statins. After controlling for statin use and smoking, results remained consistent, showing statistically significant differences of the 8-epi-PGF2{alpha} levels in all compartments between the CHD, the dilative CMP, and the ischemic CMP groups, again increasing with deterioration of disease (see Table 4). No such controlled analysis was available for the control group, as there was no statin use within this healthy population.

After performing linear regression by controlling for smoking and statin use, LVEF proved to be an independent predictor for increased 8-epi-PGF2{alpha} levels in all investigated compartments (see Table 5).


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  		Table 5 8-Epi-PGF2{alpha} linear regression analysis controlling for smoking and statin use

 

   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
Determination of 8-epi-PGF2{alpha} by immunohistochemistry and radioimmunological techniques revealed increased concentrations of 8-epi-PGF2{alpha} in the intima and media of coronary arteries in patients with ischemic CMP vs. dilated CMP and respective controls [7], with the difference between groups being significant.

Isoprostanes are a family of stable compounds produced from polyunsaturated fatty acids via a cyclooxygenase-independent, free radical-catalyzed mechanism in situ. The here investigated 8-epi-PGF2{alpha} is a prostaglandin F2{alpha} isomer derived from arachidonic acid, being presumably released into biological fluids through a phospholipase-mediated pathway and consequently excreted by urine. Isoprostanes, which can be detected in free forms in biological fluids and esterified in LDLs and cell membranes, have proven to be reliable indicators of in vivo oxidation injury [11]. In contrast to assays directed against nonspecific or unstable compounds such as lipid hydroxyperoxide-reactive aldehydes, conjugated dienes, exhaled pentanes, and malondialdehydes [9,20,21], the vasoconstrictory [22], proliferative [23], mitogenic [24], and mild proaggregatory [25] role of 8-epi-PGF2{alpha} makes it an interesting parameter in the pathophysiological understanding as well diagnosis of various diseases including atherosclerosis, ischemia reperfusion injury, and inflammatory vascular disease [1,7,8,10,19,26]. Recently, Mallat et al. [8] were able to show that 8-epi-PGF2{alpha} is increased in the pericardial fluid of heart failure patients, with the respective concentrations revealing a strong correlation between function and severity of the disease. Our own findings were able to confirm these data as we demonstrated an association of CMP and enhanced 8-epi-PGF2{alpha} levels in the plasma, serum, saliva, and urine of these patients. According to previous investigations showing that PGF2{alpha} isomers are primarily formed from cyclooxygenase-independent oxidative transformation of arachidonic acid [8,27–30], the subgroup of patients treated with ASA did not reveal a difference in 8-epi-PGF2{alpha} concentration in any of the compartments examined.

Hypercholesterolemia and oxidation of LDL have been identified to play a critical role in oxidation injury. Statins reduce enhanced plasma levels of LDL and alter the structure of the LDL particles, thus inducing an increased resistance of LDL to peroxidation. Furthermore, statins may inhibit NAD(P)H oxidase and consequently lead to a decreased generation of reactive oxygen species [31–33]. A decrease of 8-epi-PGF2{alpha} in serum and urine during treatment with statins has been reported [7,34,35], and can be attributed to the above mentioned mechanisms; therefore, we adjusted our analysis for statin use, with consistent results.

Patients within the different groups were matched according to their risk factor profile; therefore, no statistically significant difference concerning hypertension in a subgroup analysis was found either.

In previous investigations, we were able to identify an elevation of 8-epi-PGF2{alpha} levels in nonsmoking healthy adults who exposed themselves to tobacco [36]. Furthermore, a decrease of 8-epi-PGF2{alpha} to normal levels 1–2 weeks after quitting cigarette smoking and a consequent reincrease after restarting [37,38] were observed, thus emphasizing the impact of tobacco on oxidation injury. We observed a similar positive correlation between elevated 8-epi-PGF2{alpha} and smoking status in the current study; however, after adjusting for smoking, the statistically significant differences between the groups remained valid.

There was a clear increase in 8-epi-PGF2{alpha} with deteriorating heart failure, as demonstrated by a linear regression model we performed, clearly indicating that after adjustment for statin use and smoking, LVEF proved to be an independent predictor of increased 8-epi-PGF2{alpha} levels in all the investigated compartments (see Table 5). According to that, the elevation of 8-epi-PGF2{alpha}, reflecting the extent of oxidative injury in vivo, may play a significant role in the progression from asymptomatic to symptomatic heart failure and in a constant deterioration of functional capacity. Whether oxidation injury is a primary or secondary event, however, needs to be established so far.

As already mentioned, 8-epi-PGF2{alpha} exhibits a potent vasoconstrictor activity in vivo [22,39–41]. This may contribute to the enhanced peripheral and pulmonary vascular tone seen in cardiac failure and consequently exert a negative influence upon intracardiac and subendocardial blood flow, thus leading to the limited functional capacity and further deterioration of the clinical condition observed in these patients. The inverse relationship of 8-epi-PGF2{alpha} levels and LVEF supports this claim. As for the potential effect of oxidative stress on ventricular remodelling, in contrast to the results presented by Mallat et al. [8], we were not able to observe a significant difference of 8-epi-PGF2{alpha} between ischemic and dilative CMP. In our study, although we did not see a correlation between the extent of myocardial dilation and 8-epi-PGF2{alpha} concentrations in either compartment, a potential relationship cannot be ruled out and definitely requires further investigation in a different setting.


   5. Conclusion
Top
 Notes
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
In conclusion, this is the first study demonstrating an increase of 8-epi-PGF2{alpha} in the plasma, serum, saliva, and urine of patients with CHD, as well as ischemic and dilative CMP, the respective values being positively related to the severity of the disease. Reflecting the extent of oxidation injury in vivo, 8-epi-PGF2{alpha} represents a new potential noninvasive parameter for diagnosis and monitoring of patients with CHD and chronic heart failure, as well as the evaluation of a potential therapeutic benefit. Referring to CMP as a state of oxidative stress in vivo, the positive influence of antioxidative supplementation should be the issue of future investigations.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
1 Dr. Anthony Oguogho was on sabbatical leave from the Department of Physiology, Edo State University of Basic Sciences, Ekpoma, Nigeria, and was supported by a stipendium of the ÖAAD (Austrian Academic Exchange Division). Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 

  1. Montuschi P., Ciabattoni G., Paredi P., Pantelidis P., duBois R.M., Kharitonov S.A., et al. 8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. Am. J. Respir. Crit. Care Med. (1998) 158:1524–1527.[Abstract/Free Full Text]
  2. Mezzetti A., Cipollone F., Cuccurullo F. Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm. Cardiovasc. Res. (2000) 47:475–488.[Abstract/Free Full Text]
  3. McMurray J., Chopra M., Abdullah I., Smith W.E., Dargie H.J. Evidence of oxidative stress in chronic heart failure in humans. Eur. Heart J. (1993) 14:1493–1498.[Abstract/Free Full Text]
  4. Diaz-Velez C.R., Garcia-Castineiras S., Mendoza-Ramos E., Hernandez-Lopez E. Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am. Heart J. (1996) 131:146–152.[CrossRef][Web of Science][Medline]
  5. Reckelhoff J.F., Hennington B.S., Kanji V., Racusen L.C., Schmidt A.M., Yan S.D., et al. Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats. Am. J. Hypertens. (1999) 12:492–498.[CrossRef][Web of Science][Medline]
  6. Reckelhoff J.F., Zhang H., Srivastava K., Roberts L.J. II, Morrow J.D., Romero J.C. Subpressor doses of angiotensin II increase plasma F(2)-isoprostanes in rats. Hypertension (2000) 35:476–479.[Abstract/Free Full Text]
  7. Mehrabi M.R., Ekmekcioglu C., Tatzber F., Oguogho A., Ullrich R., Morgan A., et al. The isoprostane, 8-epi-PGF2 alpha, is accumulated in coronary arteries isolated from patients with coronary heart disease. Cardiovasc. Res. (1999) 43:492–499.[CrossRef][Web of Science][Medline]
  8. Mallat Z., Philip I., Lebret M., Chatel D., Maclouf J., Tedgui A. Elevated levels of 8-iso-prostaglandin F2 alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation (1998) 97:1536–1539.[Abstract/Free Full Text]
  9. Delanty N., Reilly M.P., Pratico D., Lawson J.A., McCarthy J.F., Wood A.E., et al. 8-Epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo. Circulation (1997) 95:2492–2499.[Abstract/Free Full Text]
  10. Morrow J.D., Roberts L.J. The isoprostanes: unique bioactive products of lipid peroxidation. Prog. Lipid Res. (1997) 36:1–21.[CrossRef][Web of Science][Medline]
  11. Patrono C., FitzGerald G.A. Isoprostanes: potential markers of oxidant stress in atherothrombotic disease. Arterioscler. Thromb. Vasc. Biol. (1997) 17:2309–2315.[Abstract/Free Full Text]
  12. Lawson J.A., Rokach J., FitzGerald G.A. Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J. Biol. Chem. (1999) 274:24441–24444.[Free Full Text]
  13. Pratico D. F(2)-isoprostanes: sensitive and specific non-invasive indices of lipid peroxidation in vivo. Atherosclerosis (1999) 147:1–10.[CrossRef][Web of Science][Medline]
  14. Souvignet C., Cracowski J.L., Stanke-Labesque F., Bessard G. Are isoprostanes a clinical marker for antioxidant drug investigation? Fundam. Clin. Pharmacol. (2000) 14:1–10.[Web of Science][Medline]
  15. Palombo C., Lubrano V., Sampietro T. Oxidative stress, F2-isoprostanes and endothelial dysfunction in hypercholesterolemia. Cardiovasc. Res. (1999) 44:474–476.[Free Full Text]
  16. Cracowski J.L., Stanke-Labesque F., Bessard G. Isoprostanes: new markers of oxidative stress. Fundamental and clinical aspects. Rev. Med. Intern. (2000) 21:304–307.
  17. Janssen L.J. Isoprostanes: generation, pharmacology, and roles in free-radical-mediated effects in the lung. Pulm. Pharmacol. Ther. (2000) 13:149–155.[CrossRef][Web of Science][Medline]
  18. Pilz H., Oguogho A., Chehne F., Lupattelli G., Palumbo B., Sinzinger H. Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane). Thromb. Res. (2000) 99:209–221.[CrossRef][Web of Science][Medline]
  19. Roberts L.J., Morrow J.D. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic. Biol. Med. (2000) 28:505–513.[CrossRef][Web of Science][Medline]
  20. Cracowski J.L., Tremel F., Marpeau C., Baguet J.P., Stanke-Labesque F., Mallion J.M., et al. Increased formation of F(2)-isoprostanes in patients with severe heart failure. Heart (2000) 84:439–440.[Free Full Text]
  21. Cailleux A., Allain P. Is pentane a normal constituent of human breath? Free Radic. Res. Commun. (1993) 18:323–327.[Web of Science][Medline]
  22. Kromer B.M., Tippins J.R. Coronary artery constriction by the isoprostane 8-epi prostaglandin F2 alpha. Br. J. Pharmacol. (1996) 119:1276–1280.[Web of Science][Medline]
  23. Yura T., Fukunaga M., Khan R., Nassar G.N., Badr K.F., Montero A. Free-radical-generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells. Kidney Int. (1999) 56:471–478.[CrossRef][Web of Science][Medline]
  24. Mohler E.R., Franklin M.T., Adam L.P. Intracellular signaling by 8-epi-prostaglandin F2 alpha is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries. Biochem. Biophys. Res. Commun. (1996) 225:915–923.[CrossRef][Web of Science][Medline]
  25. Leitinger N., Blazek I., Sinzinger H. The influence of isoprostanes on ADP-induced platelet aggregation and cyclic AMP-generation in human platelets. Thromb. Res. (1997) 86:337–342.[CrossRef][Web of Science][Medline]
  26. Nourooz-Zadeh J., Pereira P. F(2) isoprostanes, potential specific markers of oxidative damage in human retina. Ophthalmic Res. (2000) 32:133–137.[CrossRef][Web of Science][Medline]
  27. Morrow J.D., Hill K.E., Burk R.F., Nammour T.M., Badr K.F., Roberts L.J. II. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc. Natl. Acad. Sci. U. S. A. (1990) 87:9383–9387.[Abstract/Free Full Text]
  28. Pratico D., Lawson J.A., FitzGerald G.A. Cyclooxygenase-dependent formation of the isoprostane, 8-epi prostaglandin F2 alpha. J. Biol. Chem. (1995) 270:9800–9808.[Abstract/Free Full Text]
  29. Morrow J.D., Awad J.A., Boss H.J., Blair I.A., Roberts L.J. II. Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. Proc. Natl. Acad. Sci. U. S. A. (1992) 89:10721–10725.[Abstract/Free Full Text]
  30. Patrignani P., Santini G., Panara M.R., Sciulli M.G., Greco A., Rotondo M.T., et al. Induction of prostaglandin endoperoxide synthase-2 in human monocytes associated with cyclo-oxygenase-dependent F2-isoprostane formation. Br. J. Pharmacol. (1996) 118:1285–1293.[Web of Science][Medline]
  31. Lavy A., Brook G.J., Dankner G., Ben Amotz A., Aviram M. Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. Metabolism (1991) 40:794–799.[CrossRef][Web of Science][Medline]
  32. Hussein O., Schlezinger S., Rosenblat M., Keidar S., Aviram M. Reduced susceptibility of low-density lipoprotein (LDL) to lipid peroxidation after fluvastatin therapy is associated with the hypocholesterolemic effect of the drug and its binding to the LDL. Atherosclerosis (1997) 128:11–18.[CrossRef][Medline]
  33. Cominacini L., Pastorino A.M., Garbin U., Campagnola M., de Santis A., Davoli A., et al. The susceptibility of low-density lipoprotein to in vitro oxidation is increased in hypercholesterolemic patients. Nutrition (1994) 10:527–531.[Web of Science][Medline]
  34. Sobal G., Sinzinger H. Prostaglandins and lipid modification. Curr. Pharm. Des. (2001) 7:461–474.[CrossRef][Web of Science][Medline]
  35. Oguogho A., Sinzinger H. Isoprostanes in atherosclerosis. J. Physiol. Pharmacol. (2000) 51:673–682.[Web of Science][Medline]
  36. Wolfram R.M., Chehne F., Oguogho A., Sinzinger H. Narghile (water pipe) smoking influences platelet function and (iso-)eicosanoids. Life Sci. (2003) 74:47–53.[CrossRef][Web of Science][Medline]
  37. Chehne F., Oguogho A., Lupattelli G., Palumbo B., Sinzinger H. Effect of giving up cigarette smoking and restarting in patients with clinically manifested atherosclerosis. Prostaglandins, Leukot. Essent. Fat. Acids (2002) 67:333–339.[CrossRef]
  38. Chehne F., Oguogho A., Lupattelli G., Budinsky A.C., Palumbo B., Sinzinger H. Increase of isoprostane 8-epi-PGF(2 alpha)after restarting smoking. Prostaglandins, Leukot. Essent. Fat. Acids (2001) 64:307–310.[CrossRef]
  39. Takahashi K., Nammour T.M., Fukunaga M., Ebert J., Morrow J.D., Roberts L.J. II, et al. Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2 alpha, in the rat. Evidence for interaction with thromboxane A2 receptors. J. Clin. Invest. (1992) 90:136–141.[Web of Science][Medline]
  40. Hoffman S.W., Moore S., Ellis E.F. Isoprostanes: free radical-generated prostaglandins with constrictor effects on cerebral arterioles. Stroke (1997) 28:844–849.[Abstract/Free Full Text]
  41. Truog W.E., Norberg M., Thibeault D.W. Effects of 8-epi-prostaglandin F2 alpha and U46,619 on pulmonary hemodynamics in piglets. Biol. Neonat. (1997) 71:306–316.[Web of Science]

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