Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats

Jan Neckář, Md Abdul Hye Khan, Garrett J. Gross, Michaela Cyprová, Jaroslav Hrdlička, Alena Kvasilová, John R. Falck, William B. Campbell, Lenka Sedláková, Šárka Škutová, Veronika Olejníčková, Martina Gregorovičová, David Sedmera, František Kolář, John D. Imig

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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.

Original languageEnglish (US)
Pages (from-to)939-951
Number of pages13
JournalClinical science
Volume133
Issue number8
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Medicine(all)

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    Neckář, J., Abdul Hye Khan, M., Gross, G. J., Cyprová, M., Hrdlička, J., Kvasilová, A., Falck, J. R., Campbell, W. B., Sedláková, L., Škutová, Š., Olejníčková, V., Gregorovičová, M., Sedmera, D., Kolář, F., & Imig, J. D. (2019). Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats. Clinical science, 133(8), 939-951. https://doi.org/10.1042/CS20180728