Inhibition of platelet and neutrophil phospholipase A2 by hydroxyeicosatetraenoic acids (HETEs) A novel pharmacological mechanism for regulating free fatty acid release
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Cited by (59)
Analysis of HETEs in human whole blood by chiral UHPLC-ECAPCI/HRMS
2018, Journal of Lipid ResearchCitation Excerpt :Considering that 12(R)-HETE is synthesized by cytochrome P450 in the ocular system (27) and by 12(R)-LOX in the epidermis and tonsils (28, 29), we hypothesize that low levels of serum 12(R)-HETE are formed nonenzymatically. The role of 12(S)-HETE in platelet biology is not fully understood, with studies reporting both activation (30–32) and inhibition (33, 34) of platelet aggregation. The 12-HETE has been implicated in the pathophysiology of cancer, arteriosclerosis, and diabetes (26).
Targeted profiling of arachidonic acid and eicosanoids in rat tissue by UFLC–MS/MS: Application to identify potential markers for rheumatoid arthritis
2017, TalantaCitation Excerpt :The best characterized metabolites through the COX metabolic pathway are prostaglandins (PGs) and thromboxanes (TXs): PGs can activate the transcription of inflammation-related genes and contribute to the repression of inflammatory cytokines, and TXs were able to stimulate activation of new platelets and increases platelet aggregation [4,5]. The metabolites of LOX pathway are leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs): LTs can attract leukocytes to the site of inflammation, promoting their adhesion to the inflamed and damaged tissue, and HETEs could stimulate proliferation of muscle cells through a MAPK-dependent mechanism [6,7]. Although many selective COX or LOX inhibitors have been developed as drugs to treat inflammation, some (for example, Vioxx) have been withdrawn from the market due to gastric and cardiac side effects, or lack of efficacy in clinical trials [8].
Liquid chromatography-tandem mass spectrometry for simultaneous measurement of thromboxane B2 and 12(S)-hydroxyeicosatetraenoic acid in serum
2014, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :Whole blood derived serum TXB2 levels indirectly assess the formation of TXA2 and is the most specific measure of the pharmacological effect of COX-inhibitors on platelets [1]. Whilst the role of COX-1 product in platelet function is well-understood, relatively little is known about the physiological actions of 12(S)-HETE that has been reported to be both anti-thrombotic [2] as well as pro-thrombotic [3]. Limited and conflicting data are also available concerning the role of 12-LOX products in association with cardiovascular diseases (CVD) and major cardiovascular risk factors such as hypertension [4] and diabetes [5] in human.
Analysis, physiological and clinical significance of 12-HETE: A neglected platelet-derived 12-lipoxygenase product
2014, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :For example a study performed on 12-LOX knock-out mice showed that platelets are more responsive to aggregation induced by ADP [12] and that this phenomenon is reversed by the incubation of platelets with 12-HETE. The anti-thrombotic activity of 12-HETE was first related to an inhibitory action on PLA2 activity, resulting in a diminished availability of the substrate AA [13]. Several studies were performed in order to reveal the potential effects of 12-HETE on platelet aggregation induced by different agonists.
Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities
2005, Journal of Lipid ResearchCitation Excerpt :5-HETEL was more effective than the open acid, (±)5-hydroxy-6E,8Z,11Z, 14Z-eicosatetraenoic acid, in inhibiting 5-lipoxygenase (45, 46) and in thromboxanes and prostaglandin E2 synthesis in peritoneal macrophages (47), which was attributed to the more favorable binding conformation of the lactone. ( ±)5-Hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, but not 5-HETEL, was shown to be a specific PLA2 inhibitor (48). Therefore, the presence of 5-HETEL in vivo may have an effect on cells that use PLA2, 5-lipoxygenase, and/or cyclooxygenases, and its hydrolysis by the PONs may modulate this effect.
Synthesis of keto- and hydroxydienoic compounds from linoleic acid
1997, Chemistry and Physics of Lipids