Eicosanoids in Human Heart Failure
Study Details
Study Description
Brief Summary
Our translational project aims to evaluate the role of eicosanoids in human HF.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Heart failure (HF) is the leading cause of cardiovascular hospitalizations, and with its increasing prevalence, the healthcare systems face a heart failure pandemic. Translational research findings improve our knowledge of pathophysiology and uncover therapeutic targets in HF. Natriuretic peptides represent such examples as routinely used in diagnostics and therapeutics (neprilysin inhibitor). Despite modern pharmacotherapy, including angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), the prognosis of patients, especially with advanced heart failure, remains poor. Furthermore, most medication is limited in the late stages of HF due to their hypotensive effects.
Basic research has been focused on the eicosanoids - metabolites of cytochrome P-450 (CYP)-dependent epoxygenase pathway of arachidonic acid (AA), especially epoxyeicosatrienoic acids (EETs). In the preclinical studies, it was shown that EETs importantly contribute to the regulation of cardiovascular and renal function and exert organ-protective actions. It was also proposed that intrarenal EETs operate as an endogenous compensatory system opposing increased renin-angiotensin system (RAS) activity. EETs are rapidly transformed by soluble epoxide hydrolase (sEH) to biologically inactive dihydroxyeicosatrienoic acids (DHETs). The role of eicosanoids in human HF, however, remains unclear.
Our translational project (Eicosanoids in Human Heart Failure) aims to evaluate the role of eicosanoids in human HF.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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HF Patients with heart failure. |
Diagnostic Test: Levels of EETs, DHETs and HETEs
The plasmatic concentration of EETs, DHETs, and HETEs.
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Controls Controls without heart failure. |
Diagnostic Test: Levels of EETs, DHETs and HETEs
The plasmatic concentration of EETs, DHETs, and HETEs.
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Outcome Measures
Primary Outcome Measures
- Plasmatic levels of eicosanoids [at enrollment]
EET, DHET, 20-HETE
Secondary Outcome Measures
- Mortality [2 years]
Overall mortality
Eligibility Criteria
Criteria
Inclusion Criteria:
- Heart failure
Exclusion Criteria:
- None
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University Hospital Motol | Prague | Czechia |
Sponsors and Collaborators
- University Hospital, Motol
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet. 2018 Feb 10;391(10120):572-580. doi: 10.1016/S0140-6736(17)32520-5. Epub 2017 Nov 21.
- Elmarakby AA. Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R321-30. doi: 10.1152/ajpregu.00606.2011. Epub 2011 Nov 23. Review.
- Fan F, Roman RJ. Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology. J Am Soc Nephrol. 2017 Oct;28(10):2845-2855. doi: 10.1681/ASN.2017030252. Epub 2017 Jul 12. Review.
- Fleming I. The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease. Pharmacol Rev. 2014 Oct;66(4):1106-40. doi: 10.1124/pr.113.007781. Review.
- Gawrys O, Husková Z, Baranowska I, Walkowska A, Sadowski J, Kikerlová S, Vaňourková Z, Honetschlägerová Z, Škaroupková P, Červenka L, Falck JR, Imig JD, Kompanowska-Jezierska E. Combined treatment with epoxyeicosatrienoic acid analog and 20-hydroxyeicosatetraenoic acid antagonist provides substantial hypotensive effect in spontaneously hypertensive rats. J Hypertens. 2020 Sep;38(9):1802-1810. doi: 10.1097/HJH.0000000000002462.
- Imig JD, Cervenka L, Neckar J. Epoxylipids and soluble epoxide hydrolase in heart diseases. Biochem Pharmacol. 2022 Jan;195:114866. doi: 10.1016/j.bcp.2021.114866. Epub 2021 Dec 2. Review.
- Imig JD, Elmarakby A, Nithipatikom K, Wei S, Capdevila JH, Tuniki VR, Sangras B, Anjaiah S, Manthati VL, Sudarshan Reddy D, Falck JR. Development of epoxyeicosatrienoic acid analogs with in vivo anti-hypertensive actions. Front Physiol. 2010 Dec 3;1:157. doi: 10.3389/fphys.2010.00157. eCollection 2010.
- Jamieson KL, Endo T, Darwesh AM, Samokhvalov V, Seubert JM. Cytochrome P450-derived eicosanoids and heart function. Pharmacol Ther. 2017 Nov;179:47-83. doi: 10.1016/j.pharmthera.2017.05.005. Epub 2017 May 25. Review.
- Kala P, Miklovič M, Jíchová Š, Škaroupková P, Vaňourková Z, Maxová H, Gawrys O, Kompanowska-Jezierska E, Sadowski J, Imig JD, Falck JR, Veselka J, Červenka L, Aiglová R, Vícha M, Gloger V, Táborský M. Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation. Biomedicines. 2021 Aug 20;9(8). pii: 1053. doi: 10.3390/biomedicines9081053.
- McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021 Oct 14;:.
- Sporková A, Reddy RN, Falck JR, Imig JD, Kopkan L, Sadowski J, Červenka L. Interlobular Arteries From 2-Kidney, 1-Clip Goldblatt Hypertensive Rats' Exhibit-Impaired Vasodilator Response to Epoxyeicosatrienoic Acids. Am J Med Sci. 2016 May;351(5):513-9. doi: 10.1016/j.amjms.2016.02.030. Epub 2016 Feb 23.
- Vaduganathan M, Claggett BL, Jhund PS, Cunningham JW, Pedro Ferreira J, Zannad F, Packer M, Fonarow GC, McMurray JJV, Solomon SD. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020 Jul 11;396(10244):121-128. doi: 10.1016/S0140-6736(20)30748-0. Epub 2020 May 21.
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