Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)
Regular Article6-oxo-PGF1αand 8-epi-PGF2αin human atherosclerotic vascular tissue
Abstract
Isoprostanes are a new family of compounds generated by the free radical catalyzed action on arachidonic acid. Formed during oxidation they have been claimed to be a reliable indicator of in vivo oxidation injury. We assessed the amount of 8-epi-PGF2αin human surgical specimens as compared to PGI2(via its stable metabolite 6-oxo-PGF1α), the major compound generated by vascular tissue. 8-epi-PGF2αis low in normal vascular tissue as is the 8-epi-PGF2α/6-oxo-PGF1αratio. The vessels of smokers in general exhibited an increased 8-epi-PGF2α(r=0.82) and a decreased 6-oxo-PGF1α(r=0.71). The 8-epi-PGF2α/6-oxo-PGF1αratio is, not significantly, increased in vessels derived from hyperlipidemics and hypertensives. These findings indicate that lipid peroxidation occurs within the human arterial wall as evidenced by 8-epi-PGF2α, probably further decreasing the synthesis of PGI2and promoting atherogenic mechanisms.
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Increased isoprostane content in coronary plaques obtained from vulnerable patients
2008, Prostaglandins Leukotrienes and Essential Fatty Acids8-Iso-prostaglandin F2α (8-iso-PGF2α), a representative isoprostane, is a reliable biomarker for enhanced oxidant stress in vivo. Its urinary excretion has been proposed as a risk marker in patients with coronary heart disease. Isoprostane content has not yet been well elucidated so far in human coronary plaques. The aim of this study was to evaluate content of immunoreactive 8-iso-PGF2α in directional coronary atherectomy (DCA) specimens from patients with coronary heart diseases. Twenty-seven patients with stable angina pectoris (SAP) and 8 vulnerable patients (5 patients with unstable angina pectoris and 3 with recent myocardial infarction) were subjected to DCA. The specimens from SAP consisted of 14 de novo and 13 restenotic lesions, whereas those from the vulnerable patients were all de novo lesions. Total 8-iso-PGF2α content in the DCA specimens from the vulnerable patients was significantly greater than that from patients with SAP (5.48 (2.70–10.43) versus 2.38 (1.19–4.32) ng/g tissue, median (interquartile range), P<0.05). There was no significant difference in total 8-iso-PGF2α content between de novo and restenotic lesions from patients with SAP (3.25 (1.48–5.05) versus 1.57 (0.62–2.47) ng/g tissue, respectively, P=0.895). Total 8-iso-PGF2α content in apparently normal peripheral artery specimens was only 0.34 (0.26–0.46) ng/g tissue. In conclusion, 8-iso-PGF2α was enriched in the DCA specimens from vulnerable patients, suggesting a crucial role of free radicals in formation of vulnerable plaques and a putative benefit of anti-oxidant therapy on these patients.
The biological effects of smoking water pipe on haemostasis and the eicosanoid system is unknown. Water pipe smoking is familiar to approximately 1 billion people around the world. Considering this quite impressive number, we investigated the potential effect of smoking the Narghile on oxidation injury by monitoring parameters of the (iso)eicosanoid system. Patients were allowed to smoke a water pipe once daily for 14 days. Blood was drawn from 7 healthy adult non-cigarette smoking male volunteers before and immediately after the first smoking of the water pipe and additionally after 6 hours. One and 2 weeks thereafter, blood was drawn again before and after smoking. A total of 7 blood samples was drawn during the study, and parameters of in vivo oxidation injury (8-epi-PGF2α, malondialdehyde [MDA]) and haemostasis (11-dehydro-thromboxane B2 [11-DH-TXB2]) were investigated. A single smoking session increased oxidation injury (8-epi-PGF2α: p = 0.03; MDA: p = 0.001) and 11-DH-TXB2 (p = 0.00003) significantly, and repeated daily smoking induced a persistent long-lasting oxidation injury reflected by elevated prevalues but a smaller response to the actual water pipe smoke. These findings indicate a significant increase of in vivo oxidative stress by regular water pipe smoking.
Effect of giving up cigarette smoking and restarting in patients with clinically manifested atherosclerosis
2002, Prostaglandins Leukotrienes and Essential Fatty AcidsCigarette smoking, a key risk factor for the development of vascular disease, is associated with an increased 8-epi-prostaglandin (PG) F2α. Elevated 8-epi-PGF2α has been found in vascular tissue, blood and urine as well. We examined the influence of quitting cigarette smoking in 71 patients (38 males, 33 females; aged 32–67 a) with clinically manifested atherosclerosis and various risk factors. In addition, in eight patients with hypercholesterolemia without clinical manifestation of atherosclerosis quitting smoking was monitored as well. Twenty-six of the patients with manifested atherosclerosis and five with hypercholesterolemia restarted and the isoprostanes in plasma, serum and urine were monitored in these patients as well. Quitting cigarette smoking induces an immediate decline becoming significant after 1 or 2 weeks. Restarting smoking results in an increase in 8-epi-PGF2α reaching prevalues within almost 1 week. These findings indicate that the in vivo oxidation injury associated with cigarette smoking quickly decreases after quitting but increases soon after restarting immediately.
Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F<inf>2α</inf> in smoking and nonsmoking men and women
2002, Journal of NutritionF2-isoprostanes are recently described prostaglandin F isomers produced by cyclooxygenase-independent free radical peroxidation of arachidonic acid. Their quantification in plasma and urine is a sensitive and specific indicator of lipid peroxidation and, hence, of oxidative stress in vivo. Some components of garlic are known to possess antioxidant properties. Thus, we have investigated the effect of dietary supplementation with aged garlic extract (AGE; Kyolic; Wakunaga of America, Mission Viejo, CA) on the plasma and urine concentrations of the F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α). Because smokers are exposed to increased oxidative stress, this study was performed in both smoking and nonsmoking subjects. Plasma and urine concentrations of 8-iso-PGF2α in nonsmoking individuals were 1.25 ± 0.19 nmol/L and 272 ± 53 pmol/mmol of creatinine, respectively. In age- and sex-matched smokers, plasma and urine concentrations of 8-iso-PGF2α were 58% and 85% higher, respectively. Dietary supplementation with AGE for 14 d reduced plasma and urine concentrations of 8-iso-PGF2α by 29% and 37% in nonsmokers and by 35% and 48% in smokers. Fourteen days after cessation of dietary supplementation, plasma and urine concentrations of 8-iso-PGF2α returned to values not different from those before ingestion of AGE in both groups. Thus, dietary supplementation with AGE may be useful in reducing oxidative stress in humans.
Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells
2001, Free Radical Biology and MedicineSelenium (Se) is an integral component of glutathione peroxidase and is able to detoxify peroxides that can affect arachidonic acid (AA) metabolism, thereby influencing eicosanoid biosynthesis. This study investigated the effects of oxidant stress, a consequence of Se deficiency, on eicosanoid formation and important key enzyme expression in bovine aortic endothelial cells (BAEC). Bovine aortic endothelial cells cultured in Se-deficient media and stimulated with tumor necrosis factor α or H2O2 produced significantly less prostacyclin (PGI2) and more 15-hydroxyeicosatetraenoic acid, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), and thromboxane than Se-supplemented BAEC. Additionally, reverse transcription polymerase chain reaction and immunoblotting determined that the mRNA and protein levels of the eicosanoid forming enzymes cyclooxygenase-1 (COX1), cyclooxygenase-2 (COX2), and PGI synthase were not significantly changed. The addition of 15-HPETE to Se-supplemented BAEC inhibited the production of PGI2 suggesting that the accumulation of lipid hydroperoxides during Se-deficiency may be the underlying factor in the altered eicosanoid production during Se deficiency. Furthermore, inhibition of COX and addition of PGH2 to Se-deficient or Se-supplemented BAEC still resulted in lower PGI2 formation by Se-deficient cells. Together, these results suggest that Se deficiency modifies eicosanoid production by affecting the activity of key enzymes, particularly PGI synthase, rather than their transcription or translation.
Increase of isoprostane 8-epi-PGF<inf>2α</inf> after restarting smoking
2001, Prostaglandins Leukotrienes and Essential Fatty AcidsIsoprostanes are known as reliable markers of in vivo oxidation injury. Cigarette smoking has been shown to be associated with a significant increase in 8-epi-PGF2 α, a major member of this family of compounds. Quitting smoking reduces 8-epi-PGF2 αvalues to normal within a couple of weeks only. In this follow-up we checked the 8-epi-PGF2 α, values in plasma, serum and urine in 28 people who restarted smoking after a quitting attempt of various duration. 8-epi-PGF2 αshows a certain increase after restarting smoking reaching a maximum after already 1 week. Continuation of smoking does not significantly further increase 8-epi-PGF2αThese data indicate a fast response of restarting as on quitting smoking on in vivo oxidation injury. The oxidation injury reflected by 8-epi-PGF2 αmay be a key pathogenetic mechanism in smoking-induced vascular injury.