scholarly journals Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

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.

The interaction Between Arachidonic Acid Metabolism and Homocysteine

2020 ◽  
Vol 20 ◽  
Author(s):  
Elisa Domi ◽  
Malvina Hoxha ◽  
Bianka Hoxha ◽  
Bruno Zappacosta
Keyword(s):  
Cardiovascular Disease ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Neurological Diseases ◽  
Arachidonic Acid Metabolism ◽  
Epoxyeicosatrienoic Acids ◽  
Pathological Conditions ◽  
Literature Searches ◽  
Hydroxyeicosatetraenoic Acids ◽  
Improve Health

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.

Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid

1993 ◽  
Vol 264 (2) ◽  
pp. H327-H335 ◽  
Author(s):  
M. Rosolowsky ◽  
W. B. Campbell
Keyword(s):  
Arachidonic Acid ◽  
Coronary Arteries ◽  
Vascular Tone ◽  
Epoxyeicosatrienoic Acids ◽  
Lipoxygenase Inhibitor ◽  
Physiological Processes ◽  
Coronary Vascular Tone ◽  
Cytochrome P 450 ◽  
Endothelium Dependent Relaxation

Metabolites of arachidonic acid regulate several physiological processes, including vascular tone. The purpose of this study was to determine which metabolites of arachidonic acid are produced by bovine coronary arteries and which may regulate coronary vascular tone. Arachidonic acid induced a concentration-related, endothelium-dependent relaxation [one-half maximum effective concentration (EC50) of 2 x 10(-7) M and a maximal relaxation of 91 +/- 2% at 10(-5) M] of bovine coronary arteries that were contracted with U-46619, a thromboxane mimetic. The concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of prostaglandin I2 (PGI2), increased from 82 +/- 6 to 328 +/- 24 pg/ml with arachidonic acid (10(-5) M). Treatment with the cyclooxygenase inhibitor indomethacin attenuated arachidonic acid-induced relaxations by approximately 50% and blocked the synthesis of 6-keto-PGF1 alpha. PGI2 caused a concentration-related relaxation (EC50 of 10(-8) M and a maximal relaxation of 125 +/- 11% at 10(-7) M). BW755C, a cyclooxygenase and lipoxygenase inhibitor, inhibited arachidonic acid-induced relaxation to the same extent as indomethacin. When vessels were treated with both indomethacin and BW755C, the inhibition of relaxation was the same as either inhibitor alone. SKF 525a, a cytochrome P-450 inhibitor, reduced arachidonic acid-induced relaxation by approximately 50%. When SKF 525a was given in combination with indomethacin, the relaxation by arachidonic acid was almost completely inhibited. SKF 525a inhibited the synthesis of epoxyeicosatrienoic acids (EETs).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals One-year Risks and Burdens of Incident Cardiovascular Disease in COVID-19: Cardiovascular Manifestations of Long COVID

2021 ◽  
Author(s):  
Ziyad Al-Aly ◽  
Benjamin Bowe ◽  
Yan Xie ◽  
Evan Xu
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Health ◽  
Acute Infection ◽  
Cerebrovascular Disorders ◽  
Cardiovascular Complications ◽  
Department Of Veterans Affairs ◽  
Increased Risk ◽  
Health And Disease ◽  
One Year ◽  
Incident Cardiovascular Disease

Abstract The cardiovascular complications of acute COVID-19 are well described; however, a comprehensive characterization of the post-acute cardiovascular manifestations of COVID-19 at one year has not been undertaken. Here we use the US Department of Veterans Affairs national healthcare databases to build a cohort of 151,195 people with COVID-19, 3,670,087 contemporary and 3,656,337 historical controls to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that beyond the first 30 days of infection, people with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disease. The risks and burdens were evident among those who were non-hospitalized during the acute phase of the infection and increased in a graded fashion according to care setting of the acute infection (non-hospitalized, hospitalized, and admitted to intensive care). Taken together, our results provide evidence that risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Metabolism of Arachidonic Acid to Epoxyeicosatrienoic Acids. Hydroxyeicosatetraenoic Acids, and Prostaglandins in Cultured Rat Hippocampal Astrocytes

1993 ◽  
Vol 61 (1) ◽  
pp. 150-159 ◽  
Author(s):  
Shivachar C. Amruthesh ◽  
Markus F. Boerschel ◽  
Jerry S. McKinney ◽  
Karen A. Willoughby ◽  
Earl F. Ellis
Keyword(s):  
Arachidonic Acid ◽  
Epoxyeicosatrienoic Acids ◽  
Hippocampal Astrocytes ◽  
Hydroxyeicosatetraenoic Acids

Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia

2003 ◽  
Vol 285 (5) ◽  
pp. L1099-L1105 ◽  
Author(s):  
Asma Yaghi ◽  
J. Alyce Bradbury ◽  
Darryl C. Zeldin ◽  
Sanjay Mehta ◽  
John R. Bend ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Tone ◽  
Potential Role ◽  
Pulmonary Arteries ◽  
Epoxyeicosatrienoic Acids ◽  
Rat Lung ◽  
Metabolic Products ◽  
And Control ◽  
Cytochrome P 450

We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later (44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands (51-52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats.

scholarly journals Regulation and Maintenance of Vascular Tone and Patency in Cardiovascular Health and Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-2
Author(s):  
John W. Calvert ◽  
Christopher G. Kevil ◽  
Matthew R. Spite
Keyword(s):  
Vascular Tone ◽  
Cardiovascular Health ◽  
Health And Disease

scholarly journals The Endothelial Glycocalyx as a Double-Edged Sword in Microvascular Homeostasis and Pathogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Nuria Villalba ◽  
Sheon Baby ◽  
Sarah Y. Yuan
Keyword(s):  
Vascular Tone ◽  
Cardiovascular Health ◽  
Degradation Products ◽  
Endothelial Glycocalyx ◽  
Pharmacological Interventions ◽  
Pathogenic Factors ◽  
Health And Disease ◽  
And Function ◽  
And Control ◽  
Circulating Levels

Expressed on the endothelial cell (EC) surface of blood vessels, the glycocalyx (GCX), a mixture of carbohydrates attached to proteins, regulates the access of cells and molecules in the blood to the endothelium. Besides protecting endothelial barrier integrity, the dynamic microstructure of the GCX confers remarkable functions including mechanotransduction and control of vascular tone. Recently, a novel perspective has emerged supporting the pleiotropic roles of the endothelial GCX (eGCX) in cardiovascular health and disease. Because eGCX degradation occurs in certain pathological states, the circulating levels of eGCX degradation products have been recognized to have diagnostic or prognostic values. Beyond their biomarker roles, certain eGCX fragments serve as pathogenic factors in disease progression. Pharmacological interventions that attenuate eGCX degradation or restore its integrity have been sought. This review provides our current understanding of eGCX structure and function across the microvasculature in different organs. We also discuss disease or injury states, such as infection, sepsis and trauma, where eGCX dysfunction contributes to severe inflammatory vasculopathy.

scholarly journals P-450 Eicosanoids: A Novel Signaling Pathway Regulating Renal Function

Physiology ◽  
1999 ◽  
Vol 14 (6) ◽  
pp. 238-242
Author(s):  
Richard J. Roman ◽  
Magdalena Alonso-Galicia
Keyword(s):  
Renal Function ◽  
Arachidonic Acid ◽  
Vascular Tone ◽  
Second Messengers ◽  
Epoxyeicosatrienoic Acids ◽  
Sodium Reabsorption ◽  
Loop Of Henle ◽  
Renal Vascular ◽  
Cytochrome P 450 ◽  
Renal Vascular Tone

Cytochrome P-450 enzymes primarily metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) in the kidney. These compounds serve as second messengers that play a central role in the regulation of renal vascular tone and sodium reabsorption in the proximal tubule and thick ascending loop of Henle.

scholarly journals EDHF function in the ductus arteriosus: evidence against involvement of epoxyeicosatrienoic acids and 12S-hydroxyeicosatetraenoic acid

2009 ◽  
Vol 297 (6) ◽  
pp. H2161-H2168 ◽  
Author(s):  
Barbara Baragatti ◽  
Michal Laniado Schwartzman ◽  
Debora Angeloni ◽  
Francesca Scebba ◽  
Enrica Ciofini ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Arachidonic Acid ◽  
Ductus Arteriosus ◽  
Epoxyeicosatrienoic Acids ◽  
Spectrometric Analysis ◽  
Hydroxyeicosatetraenoic Acid ◽  
Acid Product ◽  
Acid Metabolites ◽  
Cytochrome P 450

We have previously shown (Ref. 2 ) that endothelium-derived hyperpolarizing factor (EDHF) becomes functional in the fetal ductus arteriosus on removal of nitric oxide and carbon monoxide. From this, it was proposed that EDHF originates from a cytochrome P-450 (CYP450)-catalyzed reaction being inhibited by the two agents. Here, we have examined in the mouse ductus whether EDHF can be identified as an arachidonic acid product of a CYP450 epoxygenase and allied pathways. We did not detect transcripts of the mouse CYP2C subfamily in vessel, while CYP2J subfamily transcripts were expressed with CYP2J6 and CYP2J9. These CYP2J hemoproteins were also detected in the ductus by immunofluorescence microscopy, being colocalized with the endoplasmic reticulum in both endothelial and muscle cells. Distinct CYP450 transcripts were also detected and were responsible for ω-hydroxylation (CYP4A31) and 12R-hydroxylation (CYP4B1). Mass spectrometric analysis showed formation of epoxyeicosatrienoic acids (EETs) in the intact ductus, with 11,12- and 14,15-EETs being more prominent than 5,6- and 8,9-EETs. However, their yield did not increase with nitric oxide/carbon monoxide suppression, nor did it abate with endothelium removal. No evidence was obtained for formation of 12R-hydroxyeicosatrienoic acid and ω-hydroxylation products. 2S-hydroxyeicosatetraenoic acid was instead detected, and, contrary to data implicating this compound as an alternative EDHF, its suppression with baicalein did not modify the EDHF-mediated relaxation to bradykinin. We conclude that none of the more common CYP450-linked arachidonic acid metabolites appears to qualify as EDHF in mouse ductus. We speculate that some novel eicosanoid or a totally unrelated compound requiring CYP450 for its synthesis accounts for EDHF in this vessel.

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