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

Clin Sci (Lond). 2019 Apr 29;133(8):939-951. doi: 10.1042/CS20180728. Print 2019 Apr 30.

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.

Keywords: blood pressure; epoxyeicosatrienoic acid; heart failure; myocardial infarction; spontaneously hypertensive rat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Arachidonic Acids
  • Heme Oxygenase-1