Journal
CLINICAL SCIENCE
Volume 133, Issue 8, Pages 939-951Publisher
PORTLAND PRESS LTD
DOI: 10.1042/CS20180728
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Funding
- Ministry of Health of the Czech Republic [15-27735A]
- National Institute of Health (NIH) [HL111392, DK103616, HL132908]
- Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A. the Trustee Grant
- Robert A. Welch Foundation [I-0011]
- [67985823]
- [00023001]
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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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