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Progress in Lipid Research Apr 2022Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by... (Review)
Review
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.
Topics: Eicosanoids; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Oxylipins
PubMed: 35508275
DOI: 10.1016/j.plipres.2022.101165 -
International Journal of Molecular... Nov 2021Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP)... (Review)
Review
Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, and lipid oxygenase (LOX) pathways to regulate complex cardiovascular function under physiological and pathological conditions. Various AA metabolites include prostaglandins, prostacyclin, thromboxanes, hydroxyeicosatetraenoic acids, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. The AA metabolites play important and differential roles in the modulation of vascular tone, and cardiovascular complications including atherosclerosis, hypertension, and myocardial infarction upon actions to different receptors and vascular beds. This article reviews the roles of AA metabolism in cardiovascular health and disease as well as their potential therapeutic implication.
Topics: Animals; Arachidonic Acid; Cardiovascular Diseases; Cardiovascular System; Humans; Lipid Metabolism; Prostaglandins
PubMed: 34769460
DOI: 10.3390/ijms222112029 -
Pharmacology Research & Perspectives Aug 2021Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available drugs with anti-inflammatory and analgesic properties. Their mechanism of action is associated with... (Review)
Review
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available drugs with anti-inflammatory and analgesic properties. Their mechanism of action is associated with the enzymes of the arachidonic acid cycle (cyclooxygenases: COX-1 and COX-2). The cyclooxygenase pathway results in the formation of prostanoids (prostaglandins [PGs], prostacyclins, and thromboxanes). It affects various structures of the human body, including the kidneys. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), as well as nephrotic syndrome and chronic kidney disease (CKD). AKI associated with the chronic consumption of NSAIDs is mainly attributed to pharmacological polytherapy and the presence of cardiovascular or hepatic comorbidities. The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2. It is suggested that both COX isoforms play opposing roles in renal function, with natriuresis increased by COX-1 inhibition followed by a drop in a blood pressure, whereas COX-2 inhibition increases blood pressure and promotes sodium retention. TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density. Therefore, nephrotic proteinuria and impairment of renal function may occur. The following article analyzes the association of NSAIDs with kidney disease based on available medical literature.
Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Nephritis, Interstitial; Renal Insufficiency, Chronic
PubMed: 34310861
DOI: 10.1002/prp2.817 -
Theranostics 2021: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively...
: Silicosis is a severe occupational lung disease. Current treatments for silicosis have highly limited availability ( lung transplantation) or, do not effectively prolong patient survival time ( lung lavage). There is thus an urgent clinical need for effective drugs to retard the progression of silicosis. : To systematically characterize the molecular changes associated with silicosis and to discover potential therapeutic targets, we conducted a transcriptomics analysis of human lung tissues acquired during transplantation, which was integrated with transcriptomics and metabolomics analyses of silicosis mouse lungs. The results from the multi-omics analyses were then verified by qPCR, western blot, and immunohistochemistry. The effect of Ramatroban on the progression of silicosis was evaluated in a silica-induced mouse model. : Wide metabolic alterations were found in lungs from both human patients and mice with silicosis. Targeted metabolite quantification and validation of expression of their synthases revealed that arachidonic acid (AA) pathway metabolites, prostaglandin D (PGD) and thromboxane A (TXA), were significantly up-regulated in silicosis lungs. We further examined the effect of Ramatroban, a clinical antagonist of both PGD and TXA receptors, on treating silicosis using a mouse model. The results showed that Ramatroban significantly alleviated silica-induced pulmonary inflammation, fibrosis, and cardiopulmonary dysfunction compared with the control group. : Our results revealed the importance of AA metabolic reprogramming, especially PGD and TXA in the progression of silicosis. By blocking the receptors of these two prostanoids, Ramatroban may be a novel potential therapeutic drug to inhibit the progression of silicosis.
Topics: Animals; Biomarkers; Case-Control Studies; Female; Humans; Lung; Male; Metabolome; Mice; Prostaglandin D2; Silicosis; Thromboxane A2; Transcriptome
PubMed: 33500731
DOI: 10.7150/thno.47627 -
Obstetrics & Gynecology Science May 2023Preeclampsia (PE) is a multisystem disorder that is an important cause of maternal and perinatal deaths. Currently, delivery is the only final treatment for PE. This...
Preeclampsia (PE) is a multisystem disorder that is an important cause of maternal and perinatal deaths. Currently, delivery is the only final treatment for PE. This practice is usually accompanied by premature birth, which inevitably increases neonatal morbidities. Aspirin is a non-selective non-steroidal anti-inflammatory drug that irreversibly inhibits cyclooxygenase enzymes involved in converting arachidonic acid to prostaglandins and thromboxane. Aspirin inhibits thromboxane A2 production via platelet aggregation, thereby increasing the prostacyclin/thromboxane A2 ratio and reducing platelet aggregation. Since the first case report of aspirin's potential use during pregnancy was reported in 1978, many studies have attempted to confirm the effect of aspirin on PE, and the results have been controversial. However, this preventive strategy is generally accepted in clinical practice. As evidence for aspirin's prevention of PE has been accumulating, a recent study investigated the effectiveness of aspirin at high doses of 150 mg, which is higher than before. However, there is an ongoing debate about how much aspirin should be used during pregnancy and when to start aspirin therapy. Guidelines for the use of prophylactic aspirin during pregnancy vary slightly among countries and groups. In this article, we review and summarize the evidence regarding the use of aspirin for PE prevention.
PubMed: 36924072
DOI: 10.5468/ogs.22261 -
International Journal of Molecular... Nov 2020Wound healing is an important process in the human body to protect against external threats. A dysregulation at any stage of the wound healing process may result in the... (Review)
Review
Wound healing is an important process in the human body to protect against external threats. A dysregulation at any stage of the wound healing process may result in the development of various intractable ulcers or excessive scar formation. Numerous factors such as growth factors, cytokines, and chemokines are involved in this process and play vital roles in tissue repair. Moreover, recent studies have demonstrated that lipid mediators derived from membrane fatty acids are also involved in the process of wound healing. Among these lipid mediators, we focus on eicosanoids such as prostaglandins, thromboxane, leukotrienes, and specialized pro-resolving mediators, which are produced during wound healing processes and play versatile roles in the process. This review article highlights the roles of eicosanoids on skin wound healing, especially focusing on the biosynthetic pathways and biological functions, i.e., inflammation, proliferation, migration, angiogenesis, remodeling, and scarring.
Topics: Animals; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Eicosanoids; Humans; Lipids; Lipoxygenases; Models, Biological; Prostaglandin-Endoperoxide Synthases; Skin; Wound Healing
PubMed: 33182690
DOI: 10.3390/ijms21228435 -
Journal of the American College of... Jul 2022
Topics: Aspirin; Blood Platelets; Humans; Thromboxane B2; Thromboxanes
PubMed: 35835497
DOI: 10.1016/j.jacc.2022.04.053 -
Marine Drugs Jul 2019Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of... (Review)
Review
Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of physiological and pathological processes, for instance muscle and blood vessel tone regulation, inflammation, signaling, hemostasis, reproduction, and sleep-wake regulation. These molecules have successively been discovered in lower organisms, including marine invertebrates in which they play similar roles to those in mammals, being involved in the control of oogenesis and spermatogenesis, ion transport, and defense. Prostaglandins have also been found in some marine macroalgae of the genera and and very recently the PGs pathway has been identified for the first time in some species of marine microalgae. In this review we report on the occurrence of prostaglandins in the marine environment and discuss the anti-inflammatory role of these molecules.
Topics: Animals; Anthozoa; Anti-Inflammatory Agents; Aquatic Organisms; Gracilaria; Laminaria; Microalgae; Prostaglandins; Thromboxanes
PubMed: 31340503
DOI: 10.3390/md17070428 -
Biomedicines Apr 2023Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the... (Review)
Review
Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A IIA (sPLA-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA-IIA levels together with eicosanoids in the sera of COVID patients. sPLA could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA-IIA in COVID-19-associated coagulopathy (CAC).
PubMed: 37189799
DOI: 10.3390/biomedicines11041181