No abstract available.
Endothelium ; Kidney Diseases ; Urethral Diseases ; Eicosanoids ; Myofibroblasts

No abstract available.
Endothelium ; Kidney Diseases ; Urethral Diseases ; Eicosanoids ; Myofibroblasts

Human mast cells are potent effector cells in host defense mechanisms of innate and acquired immunity, including inflammatory diseases such as asthma and atherosclerosis. Mast cells originate from pluripotent hematopoietic progenitors in the bone marrow. Activation of mast cells by different stimuli triggers the release of a large range of mediators, including de novo synthesized eicosanoids which are highly biologically active lipid mediators. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoids biosynthesis. The article summarizes current knowledge on mast cell biosynthesis of lipid mediator and the role in inflammation.
Adaptive Immunity ; Arachidonic Acid ; Asthma ; Atherosclerosis ; Bone Marrow ; Cytoplasm ; Defense Mechanisms ; Eicosanoids ; Humans ; Inflammation ; Mast Cells*

The article aims to study the effect and mechanism of shear stress on eicosanoids produced by the metabolism of polyunsaturated fatty acids in endothelial cells. First, human umbilical vein endothelial cells were treated by control (Static), laminar shear stress (LSS) and oscillatory shear stress (OSS) for 6 h. Then the endothelial cells were incubated with fresh M199 medium for 3 h, and the cell culture medium was collected. Ultra-performance liquid chromatography-mass spectrometer was used to detect the level of eicosanoid metabolites secreted by endothelial cells. The results showed that under different shear stress, the level of eicosanoid metabolites were changed significantly. We found 10 metabolites were significantly up-regulated by OSS compared with those in LSS group, including PGD2, PGE2, PGF2α and PGJ2 produced by cyclooxygenase; 11-HETE, 15-HETE, 13-HDoHE produced by lipoxygenase or spontaneous oxidation; 12,13-EpOME, 9,10-EpOME, 9,10-DiHOME produced by cytochrome P450 oxidase and soluble epoxide hydrolase. The transcription levels of these up-regulated eicosanoids metabolic enzyme-related genes were also increased in vitro and in vivo. These results indicate that OSS may promote the increase of metabolites by up-regulating the transcription level of metabolic enzyme-related genes, which playing a key role in the development of atherosclerosis. This study reveals the effect of shear stress on eicosanoid metabolism in endothelial cells, which provides a novel supplement to the systems biology approach to study systemic hemodynamics.
Cells, Cultured ; Eicosanoids ; Human Umbilical Vein Endothelial Cells ; Humans ; Metabolomics ; Stress, Mechanical

Eicosanoids are oxidized derivatives of 20-carbon polyunsaturated fatty acids (PUFAs). In recent years, the role and mechanism of eicosanoids in cardiovascular diseases have attracted extensive attention. Substrate PUFAs including arachidonic acid are metabolized by cyclooxygenase, lipoxygenase, cytochrome P450 oxidase enzymes, or non-enzymatic auto-oxidation. Eicosanoid metabolomics is an effective approach to study the complex metabolic network of eicosanoids. In this review, we discussed the biosynthesis and functional activities of eicosanoids, the strategies of eicosanoid metabolomics, and applications and research progress of eicosanoid metabolomics in cardiovascular diseases, which might offer new insights and strategies for the treatment of cardiovascular diseases.
Arachidonic Acid ; Cardiovascular Diseases ; Cytochrome P-450 Enzyme System ; Eicosanoids ; Humans ; Metabolomics

The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.
8,11,14-Eicosatrienoic Acid/pharmacology* ; Cardiovascular System ; Cytochrome P-450 Enzyme System ; Eicosanoids ; Endothelial Cells ; Humans

Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C₄ by platelets that adhere to granulocytes releasing leukotriene A₄. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E₂ or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E₂ is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation.
Arachidonic Acid ; Asthma ; Eicosanoids ; Eosinophils ; Granulocytes ; Humans ; Hypersensitivity ; Immunoassay ; Inflammation* ; Isoprostanes ; Leukotrienes ; Macrophages ; Oxygen ; Phenotype ; Spectrum Analysis ; Sputum

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.
Animals ; Calcium ; Cytosol ; Eicosanoids ; Inflammation ; Leukotriene C4 ; Mast Cells* ; Mice ; Mitogen-Activated Protein Kinases ; Phospholipases ; Prostaglandin D2 ; Protein Kinases

PURPOSE: It has been suggested that prostaglandins (PGs) play an important role in ischemia-reperfusion (IR) organ injury. However, the significance of PGs is not well documented for a testicular IR injury. The purpose of this study was to assess the potential role of PGs in rat testicular ischemia and IR injury MATERIALS AND METHODS: Sprague-Dawley male rats were divided into 7 groups, each containing 7 rats. The right spermatic cord was clamped with vascular clamps for 30 minute (group B, C), 90 minute (D, E) and 240 minute (F, G). Groups B, D, and F were ischemia groups and the group C, E, and G were reperfusion groups. Reperfusion was carried out after ischemia lasting 30, 90 and 240 min. The levels of thromboxane B2 (TxB2), 6-keto-PGF1alpha and prostaglandins E2 (PGE2) were measured using High-Performance Liquid Chromatography (HPLC). RESULTS: The levels of TxB2 were significantly elevated in groups D, E, F, and G than in the controls (p<0.05, each group). The TxB2 levels in the ischemia group F were significantly decreased compared to that of group D (p<0.05). The histological features shown in groups D, and F were typical ischemic changes, but atypical in groups B, and C. The most severe damage was noted in group G. These features were well matched with the changes of TxB2 in testicular ischemia and IR injury. The levels of 6-keto-PGF1alpha were significantly elevated in all the ischemia and IR groups compared to that of the controls (p<0.05). CONCLUSIONS: These results suggested that TxB2 might have an active role in testicular IR injury, although PGE2 and 6-keto-PGF1alpha seemed not to have an active role.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Dinoprostone ; Eicosanoids* ; Humans ; Ischemia ; Male ; Prostaglandins ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; Spermatic Cord ; Thromboxane B2

Ischemia and reperfusion of skeletal muscle occurs in acute vascular occlusion and revascularization, in elective vascular surgery, in upper and lower extremity surgery by means of a tourniquet, and in free transplantation of muscle containing cutaneous flaps. During revascularization of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids are released that may have a role in the pathogenesis of reperfusion injury. The exact role of eicosanoids in the imposed ischemia-reperfusion induced functional deficits in skeletal muscle is still unknown, we compared tissue edema and the changes of eicosanoids and the effects of cyclooxygenase inhibitor indomethacin in the rat right hindlimb by application of tourniquet ischemia-reperfusionn injury. After 4-hours of ischemia, reperfusion was established 4 hours by releasing tourniquet. Experimental groups comparised ischemia-reperfused animals pretreated with indomethacin 20 mg/kg. The control animals received normal saline, 4 hours of ischemia without reperfusion. To assess tissue edema, wet/dry weight ratios were determined and the concentrations of prostaglandins and thromboxane were measured by the high performance liquid chromatography with UV detector at 195 nm. Ischemia itself did not result in muscle edema and did not increase the release of cyclooxygenase metabolites, but muscle edema(52%, p<0.01), and the relase of 6-keto-PGFalpha(151%, p<0.01), thromboxane B2(98%, p<0.05), and PGE2(127%, p<0.01) were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema(35%, p<0.05 versus ischemis-reperfusion control) and decreased 6-keto-PGF1alpha(65%, p<0.05) releases. These results support view that cyclooxygenase products may play significant roles in the formation of ischemic muscle edema and suggest that nonsteroidal antiinflammatory agents and eicosanoids antagonists might be beneficial to the management of acute limb ischemia-reperfusion injury.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Chromatography, Liquid ; Edema* ; Eicosanoids* ; Extremities ; Hindlimb ; Indomethacin ; Ischemia* ; Lower Extremity ; Muscle, Skeletal* ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; Rats* ; Reperfusion Injury* ; Reperfusion* ; Tourniquets