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Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats
J. Neckář, MA. Hye Khan, GJ. Gross, M. Cyprová, J. Hrdlička, A. Kvasilová, JR. Falck, WB. Campbell, L. Sedláková, Š. Škutová, V. Olejníčková, M. Gregorovičová, D. Sedmera, F. Kolář, JD. Imig,
Language English Country Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 DK103616
NIDDK NIH HHS - United States
R01 HL111392
NHLBI NIH HHS - United States
R01 HL132908
NHLBI NIH HHS - United States
NV15-27735A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Medline Complete (EBSCOhost)
from 2010-03-01
PubMed
30979784
DOI
10.1042/cs20180728
Knihovny.cz E-resources
- MeSH
- Heme Oxygenase-1 genetics metabolism MeSH
- Myocardial Infarction drug therapy genetics metabolism physiopathology MeSH
- Blood Pressure MeSH
- Rats MeSH
- Arachidonic Acids administration & dosage chemistry MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Rats, Inbred SHR MeSH
- Heart physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After 2 weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure (SBP) and echocardiography (ECHO) measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. Fractional shortening (FS) was decreased to 18.4 ± 1.0% in vehicle-treated MI rats compared with corresponding sham (30.6 ± 1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7 ± 0.7%), markedly increased heme oxygenase-1 (HO-1) immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13 and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.
Department of Biochemistry University of Texas Southwestern Medical Center Dallas TX U S A
Department of Pharmacology and Toxicology Medical College of Wisconsin Milwaukee WI U S A
Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic
References provided by Crossref.org
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- $a Neckář, Jan $u Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, U.S.A. jan.neckar@fgu.cas.cz. Department of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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- $a Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After 2 weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure (SBP) and echocardiography (ECHO) measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. Fractional shortening (FS) was decreased to 18.4 ± 1.0% in vehicle-treated MI rats compared with corresponding sham (30.6 ± 1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7 ± 0.7%), markedly increased heme oxygenase-1 (HO-1) immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13 and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.
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