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

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.

• Authors: 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
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 133 Issue 8 Pg. 939-951 (04 30 2019) ISSN: 1470-8736 [Electronic] England
• PMID: 30979784 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chemical References

• Arachidonic Acids
• Heme Oxygenase-1

Topics

• Animals
• Arachidonic Acids (administration & dosage, chemistry)
• Blood Pressure
• Disease Models, Animal
• Heart (physiopathology)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Male
• Myocardial Infarction (drug therapy, genetics, metabolism, physiopathology)
• Rats
• Rats, Inbred SHR