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Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats. Clin Sci (Lond) 2019 Apr 30;133(8):939-951 PMID: 30979784 PMCID: PMC6492034

Pubmed ID

30979784

DOI

10.1042/CS20180728

Abstract

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.

Author List

Neckář J, Hye Khan MA, Gross GJ, Cyprová M, Hrdlička J, Kvasilová A, Falck JR, Campbell WB, Sedláková L, Škutová Š, Olejníčková V, Gregorovičová M, Sedmera D, Kolář F, Imig JD

Authors

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
John D. Imig PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Md Abdul Hye Khan PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-85064975365
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e