Epoxyeicosatrienoic acids (EETs), cytochrome P450 epoxygenase metabolites of arachidonic acid, represent a promising pharmacological approach in cardiovascular disease prevention. In our study, cardioprotective effects of a novel, stable and orally active agonistic 14,15-EET analog EET-B on the progression of post-ischemic heart failure was examined in spontaneously hypertensive rats (SHR), a pre-clinical rodent model of human essential hypertension. SHR were subjected to myocardial infarction and the effects of continuous EET-B treatment before and after MI on post-ischemic left ventricular function, myocardial fibrosis and inflammation were analyzed. As EET-based therapies can attenuate the progression of HF by mechanisms involving activation of heme oxygenase-1, its immunopositivity in viable myocytes of the ischemic myocardium was also determined. We demonstrated that EET-B treatment improved post-ischemic left ventricular function, markedly increased heme oxygenase-1 immunopositivity in cardiomyocytes subjected myocardial infarction and reduced cardiac inflammation and fibrosis. These findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce remodeling in SHR subjected to myocardial infarction.
Neckár, Jan – Khan, M. A. H. – Gross, G. J. – Cyprová, Michaela – Hrdlicka, Jaroslav – Kvasilová, A. – Falck, J. R. – Campbell, W. B. – Sedláková, Lenka – Škutová, Šárka – Olejnícková, Veronika – Gregorovicová, Martina – Sedmera, David – Kolár, František – Imig, J. D. Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats. Clinical science. Roc. 133, c. 8 (2019), s. 939-951. ISSN 0143-5221, IF: 5,237 DOI
