The interaction Between Arachidonic Acid Metabolism and Homocysteine

Purpose: Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases including cardiovascular disease (CVD), inflammation, neurological diseases, cancer and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation as shown by the development of CVD following the imbalance of its metabolites. Aim of The Review: This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. Methods: In silico literature searches were performed on PubMed and Scopus as main sources. Results: Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI₂), thromboxane (TXA), epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Conclusions: We believe that by targeting Hcy in AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for dietician to manipulate diets to improve health.

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Enhanced synthesis of epoxyeicosatrienoic acids by cholesterol-fed rabbit aorta

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.3.h843 ◽

1991 ◽

Vol 261 (3) ◽

pp. H843-H852 ◽

Cited By ~ 18

Author(s):

S. L. Pfister ◽

J. R. Falck ◽

W. B. Campbell

Keyword(s):

Arachidonic Acid ◽

Mass Spectra ◽

Acid Metabolism ◽

Rabbit Aorta ◽

Arachidonic Acid Metabolism ◽

Gas Chromatography Mass Spectrometry ◽

Epoxyeicosatrienoic Acids ◽

Aortic Tissue ◽

Cytochrome P 450 ◽

Hydroxyeicosatetraenoic Acids

Arachidonic acid metabolism via cyclooxygenase, lipoxygenase, and cytochrome P-450 epoxygenase was investigated in thoracic aortic tissue obtained from rabbits fed either standard rabbit chow or chow containing 2% cholesterol. Aortic strips were incubated with [14C]arachidonic acid and A23187. Metabolites from extracted media were resolved by high-pressure liquid chromatography (HPLC). Normal and cholesterol-fed rabbit aortas synthesized prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs). The major cyclooxygenase products were 6-keto-PGF1 alpha and PGE2. Basal aortic 6-keto-PGF1 alpha production was slightly reduced in cholesterol-fed compared with normal rabbits. 12(S)- and 15(S)-HETE were the major aortic lipoxygenase products from both normal and cholesterol-fed rabbits. The structures were confirmed by gas chromatography-mass spectrometry (GC-MS). Only cholesterol-fed rabbit aortas metabolized arachidonic acid via cytochrome P-450 epoxygenase to the epoxyeicosatrienoic acids (EETs). 14,15-, 11,12-, 8,9-, and 5,6-EET were identified based on comigration on HPLC with known 14C-labeled standards and typical mass spectra. Incubation of normal aorta with 14,15-EET decreased the basal synthesis of 6-keto-PGF1 alpha. The other EETs were without effect. The four EET regioisomers relaxed the norepinephrine-precontracted normal and cholesterol-fed rabbit aorta. The relaxation response to 14,15-EET was greater in aortas from cholesterol-fed rabbits. These studies demonstrate that hypercholesterolemia, before the development of atherosclerosis, alters arachidonic acid metabolism via both the cyclooxygenase and epoxygenase pathways.

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Use of Metabolomic Profiling in the Study of Arachidonic Acid Metabolism in Cardiovascular Disease

Congestive Heart Failure ◽

10.1111/j.1751-7133.2010.00209.x ◽

2011 ◽

Vol 17 (1) ◽

pp. 42-46 ◽

Cited By ~ 31

Author(s):

Ning Li ◽

Jun-Yan Liu ◽

Hong Qiu ◽

Todd R. Harris ◽

Padmini Sirish ◽

...

Keyword(s):

Cardiovascular Disease ◽

Arachidonic Acid ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Metabolomic Profiling

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Modulation by hydroxyeicosatetraenoic acids (HETEs) of arachidonic acid metabolism in mouse resident peritoneal macrophages

European Journal of Pharmacology ◽

10.1016/0014-2999(85)90061-5 ◽

1985 ◽

Vol 107 (2) ◽

pp. 215-222 ◽

Cited By ~ 32

Author(s):

Joseph Chang ◽

Barbara Lamb ◽

Laura Marinari ◽

Anthony F. Kreft ◽

Alan J. Lewis

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

Peritoneal Macrophages ◽

Arachidonic Acid Metabolism ◽

Hydroxyeicosatetraenoic Acids

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Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms222112029 ◽

2021 ◽

Vol 22 (21) ◽

pp. 12029

Author(s):

Yan Zhou ◽

Haroon Khan ◽

Jianbo Xiao ◽

Wai San Cheang

Keyword(s):

Arachidonic Acid ◽

Vascular Tone ◽

Cardiovascular Health ◽

Cardiovascular Complications ◽

Epoxyeicosatrienoic Acids ◽

Pathological Conditions ◽

Health And Disease ◽

Acid Metabolites ◽

Vascular Beds ◽

Hydroxyeicosatetraenoic Acids

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.

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