N-3 long chain polyunsaturated fatty acids increase the expression of PPARγ-target genes and resistance of isolated heart and cultured cardiomyocytes to ischemic injury.

Abstract

The goal of present investigation is to check the hypothesis that cardioprotective effect of polyunsaturated fatty acids (PUFAs) is mediated by influence on mRNA expression level of the FATP, IL-1ra and GJP43 through stimulation of PPARγ. Animals obtained n-3 PUFAs orally during 4 weeks (0.1ml/100g b.w. per day) or during prenatal period. In experiments, isolated perfused hearts were subjected to 20-min regional ischemia and 40min reperfusion. The hearts of newborn rats (2-3days old) were used for isolated cardiomyocytes culture preparing. Culture cells underwent 30min of anoxia followed by 60min of reoxygenation. Using rtPCR the level of FATP, IL-1ra, GJP43 and BCL2 mRNA in isolated cardiomyocyte and hearts was evaluated. The data obtained indicate that in heart tissues from pups with prenatal n-3 PUFAs application the level of LA and DHA acids were increased in 3.6-fold and 2-fold correspondingly comparing to control. In adult hearts the level of DHA was increased in 1.4-fold, and the level of EPA-in 6.9-fold. We observed the increase in mRNA level of PPARγ-target genes: FATP in 2.25 times, and IL-1ra in 8.4 times. At the same time the level of mRNA of antiapoptotic gene BCL2 was increased in 2.13 times and Connexin-43 gene in 2.2 times after n-3 PUFAs application. These effects were accompanied by significantly improved cardiac function, and increase of living cardiomyocytes number at modeling of ischemia-reperfusion. n-3 PUFAs application has cardioprotective effects and increases mRNA level of FATP, IL-1ra, GJP43, and BCL2 genes in culture of neonatal cardiomyocytes and in adult hearts.