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Advances in Pharmacology (San Diego,... 2023Myocardial disease, the abnormalities of the cardiac muscle, is the leading cause of death in humans. Eicosanoids represent a large spectrum of lipid mediators with...
Myocardial disease, the abnormalities of the cardiac muscle, is the leading cause of death in humans. Eicosanoids represent a large spectrum of lipid mediators with critical roles in physiological and pathophysiological conditions. Arachidonic acid (AA) is the major resource of eicosanoids and is metabolized via cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP) enzymes producing a diverse family of lipid mediators called eicosanoids, including prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Beyond the well-established roles of eicosanoids in inflammation and vascular biology, a growing body of evidence showed that eicosanoids, especially CYP450 derived eicosanoids EETs, are preventive and therapeutic targets for many of the myocardial diseases. EETs not only ameliorate the cardiac injury and remodeling in different pathological models, but also attenuate subsequent hemodynamic disturbances and cardiac dysfunction. EETs have direct and indirect protective properties in the myocardium, and thus relieve dietetic cardiomyopathy and inflammatory cardiomyopathy. Moreover, EETs are capable to attenuate the ischemic cardiomyopathy, including the myocardial infarction and cardiac ischemic reperfusion injury. Multiple biological events and signaling networks are targeted during the myocardial protection of EETs, these are including mitochondria hemostasis, angiogenesis, oxidative stress, inflammatory response, metabolic regulation, endoplasmic reticulum (ER) stress and cell death. Additionally, eicosanoids from COX and LOX also have important roles in some of the myocardial diseases, such as cardiac hypertrophy and ischemic heart disease. This chapter summarizes the physiological and pathophysiological significance, and the signal mechanisms of the eicosanoids, especially the EETs, in myocardial diseases.
Topics: Humans; Eicosanoids; Arachidonic Acid; Cytochrome P-450 Enzyme System; Inflammation; Cardiomyopathies
PubMed: 37236758
DOI: 10.1016/bs.apha.2022.11.001 -
Nutrients Feb 2022Nutrition is important in cystic fibrosis (CF) because the disease is associated with a higher energy consumption, special nutritional deficiencies, and malabsorption... (Review)
Review
Nutrition is important in cystic fibrosis (CF) because the disease is associated with a higher energy consumption, special nutritional deficiencies, and malabsorption mainly related to pancreatic insufficiency. The clinical course with deterioration of lung function has been shown to relate to nutrition. Despite general recommendation of high energy intake, the clinical deterioration is difficult to restrain suggesting that special needs have not been identified and specified. It is well-known that the CF phenotype is associated with lipid abnormalities, especially in the essential or conditionally essential fatty acids. This review will concentrate on the qualitative aspects of fat metabolism, which has mainly been neglected in dietary fat recommendations focusing on fat quantity. For more than 60 years it has been known and confirmed that the patients have a deficiency of linoleic acid, an n-6 essential fatty acid of importance for membrane structure and function. The ratio between arachidonic acid and docosahexaenoic acid, conditionally essential fatty acids of the n-6 and n-3 series, respectively, is often increased. The recently discovered relations between the CFTR modulators and lipid metabolism raise new interests in this field and together with new technology provide possibilities to specify further specify personalized therapy.
Topics: Arachidonic Acid; Cystic Fibrosis; Docosahexaenoic Acids; Fatty Acids, Essential; Humans; Linoleic Acid
PubMed: 35215502
DOI: 10.3390/nu14040853 -
Journal of Agricultural and Food... Mar 2021It is essential to analyze the metabolism of dietary polyunsaturated fatty acids in the brain for the research and development of functional foods. In this study, a...
It is essential to analyze the metabolism of dietary polyunsaturated fatty acids in the brain for the research and development of functional foods. In this study, a single dose of 2,2-dideuterium-labeled docosatetraenoic acid ((+2)DTA) or 2,2-dideuterium-labeled arachidonic acid ((+2)AA) was orally administered to Institute of Cancer Research (ICR) mice and its metabolism in the brain was investigated. In the (+2)DTA group, the (+2)DTA content in the brain was significantly increased at 4, 8, 24, and 96 h compared to 0 h after administration, while in the (+2)AA group, the (+2)AA content was significantly increased at 4, 8, 24, and 96 h compared to 0 h. However, there was no significant difference in the content of (+2)DTA, a metabolite of (+2)AA, among all the groups. These results suggest that dietary (+2)DTA and (+2)AA pass through the blood-brain barrier and dietary (+2)AA is rather stored in the brain than converted to (+2)DTA.
Topics: Animals; Arachidonic Acid; Brain; Diet; Fatty Acids, Unsaturated; Mice
PubMed: 33594883
DOI: 10.1021/acs.jafc.0c07916 -
Critical Reviews in Food Science and... 2021Arachidonic acid (ARA), an n-6 essential fatty acid, plays an important role in human and animal growth and development. The ARA presents in the membrane phospholipids... (Review)
Review
Arachidonic acid (ARA), an n-6 essential fatty acid, plays an important role in human and animal growth and development. The ARA presents in the membrane phospholipids can be released by phospholipase A2. These free arachidonic acid molecules are then used to produce eicosanoids through three different pathways. Previous studies have demonstrated that eicosanoids have a wide range of physiological functions. Although they are generally considered to be pro-inflammatory molecules, recent advances have elucidated they have an effect on innate immunity via regulating the development, and differentiation of innate immune cells and the function of the intestinal epithelial barrier. Here, we review eicosanoids generation in intestine and their role in intestinal innate immunity, focusing on intestinal epithelial barrier, innate immune cell in lamina propria (LP) and their crosstalk.
Topics: Animals; Arachidonic Acid; Cell Differentiation; Eicosanoids; Humans; Immunity, Innate; Intestines
PubMed: 32662287
DOI: 10.1080/10408398.2020.1777932 -
Nutrients Mar 2021The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are... (Review)
Review
The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present review analyzes the neuroprotective role of DHA and AA in the extreme stages of life, emphasizing the importance of these LCPUFA during the first year of life and in the developing/prevention of neurodegenerative diseases associated with aging.
Topics: Aging; Arachidonic Acid; Brain; Docosahexaenoic Acids; Humans; Life Cycle Stages; Neurodegenerative Diseases; Neurogenesis; Neuroprotective Agents; Nutrients; Signal Transduction
PubMed: 33803760
DOI: 10.3390/nu13030986 -
Free Radical Biology & Medicine Nov 2022Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in...
Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in the acute phase of SCI remains elusive. Here we quantified AA metabolomics by High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Method (LC-MS/MS) using spinal cord tissue collected at 4 h, 24 h and 48 h after contusive SCI in rats. Remarkably, Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) were significantly increased throughout the acute SCI. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the key enzymes involved in the production of PGE2 and LTB4, were elevated in the lesioned spinal cord tissue, validated by both western blot and immunofluorecnce. The spatial-temporal changes of COX-2 and 5-LOX mainly occurs in neurons both in epicenter and rostral and caudal spinal cord segments after SCI. Our study sheds light on the dynamic microenvironment changes in acute SCI by characterizing the profile of AA metabolism. The COX-2 and 5-LOX may be promising therapeutic target for SCI.
Topics: Rats; Animals; Cyclooxygenase 2; Chromatography, Liquid; Arachidonic Acid; Leukotriene B4; Dinoprostone; Tandem Mass Spectrometry; Up-Regulation; Metabolomics; Spinal Cord Injuries
PubMed: 36272669
DOI: 10.1016/j.freeradbiomed.2022.10.303 -
Journal of Thrombosis and Haemostasis :... Sep 2023Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory...
BACKGROUND
Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization.
OBJECTIVES
The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathologic results.
METHODS
An international multicenter study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator that we supplied.
RESULTS
We report variability in the potency (P) of activators in comparison with the comparator. Thrombin receptor activating peptide 6 (P, 1.32-2.68), arachidonic acid (P, 0.87-1.43), and epinephrine (P, 0.97-1.34) showed the greatest variability. ADP (P, 1.04-1.20) and ristocetin (P, 0.98-1.07) were the most consistent. The data highlighted clear interindividual variability, notably for ADP and epinephrine. Four profiles of responses were observed with ADP from high-responders, intermediate-responders, and low-responders. A fifth profile corresponding to nonresponders (5% of the individuals) was observed with epinephrine.
CONCLUSION
Based on these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.
Topics: Humans; Platelet Aggregation; Ristocetin; Arachidonic Acid; Reproducibility of Results; Adenosine Diphosphate; Platelet Function Tests; Platelet Aggregation Inhibitors; Epinephrine; Communication; Blood Platelets
PubMed: 37331519
DOI: 10.1016/j.jtha.2023.05.027 -
Circulation Research Jun 2024Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence... (Review)
Review
Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.
Topics: Humans; Arachidonic Acid; Animals; Cardiovascular Diseases; Signal Transduction; Metabolic Diseases; Cardiometabolic Risk Factors; Obesity
PubMed: 38900855
DOI: 10.1161/CIRCRESAHA.124.324383 -
Biological & Pharmaceutical Bulletin May 2022Plasmalogens are a group of glycerophospholipids containing a vinyl-ether bond at the sn-1 position in the glycerol backbone. Cellular membrane plasmalogens are...
Plasmalogens are a group of glycerophospholipids containing a vinyl-ether bond at the sn-1 position in the glycerol backbone. Cellular membrane plasmalogens are considered to have important roles in homeostasis as endogenous antioxidants, differentiation, and intracellular signal transduction pathways including neural transmission. Therefore, reduced levels of plasmalogens have been suggested to be associated with neurodegenerative diseases such as Alzheimer's disease. Interestingly, although arachidonic acid is considered to be involved in learning and memory, it could be liberated and excessively activate neuronal activity to the excitotoxic levels seen in Alzheimer's disease patients. Here, we examined the protective effects of several kinds of plasmalogens against cellular toxicity caused by arachidonic acid in human neuroblastoma SH-SY5Y cells. As a result, only phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) showed protective effects against arachidonic acid-induced cytotoxicity based on the results of lactate dehydrogenase release and ATP depletion assays, as well as cellular morphological changes in SH-SY5Y cells. These results indicate that PC-PLS-18 protects against arachidonic acid-induced cytotoxicity, possibly via improving the stability of the cellular membrane in SH-SY5Y cells.
Topics: Alzheimer Disease; Arachidonic Acid; Humans; Lecithins; Oleic Acid; Plasmalogens
PubMed: 35236811
DOI: 10.1248/bpb.b22-00035 -
Pharmacology & Therapeutics Jun 2022Cytochrome P450 (CYP) enzymes are frequently referred to as the third pathway for the metabolism of arachidonic acid. While it is true that these enzymes generate... (Review)
Review
Cytochrome P450 (CYP) enzymes are frequently referred to as the third pathway for the metabolism of arachidonic acid. While it is true that these enzymes generate arachidonic acid epoxides i.e. the epoxyeicosatrienoic acids (EETs), they are able to accept a wealth of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) to generate a large range of regio- and stereo-isomers with distinct biochemical properties and physiological actions. Probably the best studied are the EETs which have well documented effects on vascular reactivity and angiogenesis. CYP enzymes can also participate in crosstalk with other PUFA pathways and metabolize prostaglandin G and H, which are the precursors of effector prostaglandins, to affect macrophage function and lymphangiogenesis. The activity of the PUFA epoxides is thought to be kept in check by the activity of epoxide hydrolases. However, rather than being inactive, the diols generated have been shown to regulate neutrophil activation, stem and progenitor cell proliferation and Notch signaling in addition to acting as exercise-induced lipokines. Excessive production of PUFA diols has also been implicated in pathologies such as severe respiratory distress syndromes, including COVID-19, and diabetic retinopathy. This review highlights some of the recent findings related to this pathway that affect angiogenesis and stem cell biology.
Topics: Arachidonic Acid; COVID-19; Cytochrome P-450 Enzyme System; Eicosanoids; Epoxy Compounds; Fatty Acids; Fatty Acids, Unsaturated; Humans; Neovascularization, Pathologic
PubMed: 34848204
DOI: 10.1016/j.pharmthera.2021.108049