Sage Journals: Discover world-class research

Abstract

The cardiovascular benefit of fish oil, including eicosapentaenoic acid (EPA), in humans and experimental animals has been reported. The role of endothelin-1 (ET-1) in cardiac hypertrophy is well known. Endothelin-1 stimulates prepro–ET-1 mRNA expression in cardiomyocytes, and the autocrine/paracrine system of ET-1 is important for cardiomyocyte hypertrophy. Although many studies link EPA to cardiac protection, the effect of EPA on cardiac hypertrophy has yet to be clarified. Recently, we demonstrated that ET-1–induced cardiomyocytic change could be prevented by pretreatment with EPA. The present study investigated the changes of different components of the ET system at the mRNA level in ET-1–administered cardiomyocytes, and examined the effect of EPA pretreatment. Ventricular cardiomyocytes were isolated from 2-day-old Sprague-Dawley rats, cultured in Dulbecco’s modified Eagle’s medium and Ham F12 supplemented with 0.1% fatty acid–free bovine serum albumin for 3 days. At Day 4 of culture, the cardiomyocytes were divided into 3 groups: control group, ET-1–treated (0.1 nM) group, and ET-1–treated group pretreated with EPA (10 μM). Twenty-four hours after treatment, the gene expressions of different components of the endothelin system in three experimental groups were evaluated by real-time polymerase chain reaction. Prepro–ET-1 mRNA expression was 53% upregulated in ET-1–induced hypertrophied cardiomyocytes and suppressed in the EPA-pretreated group. Endothelin-converting enzyme-1 (ECE-1) was also increased in ET-1–administered cardiomyocytes by 42% compared with the control group and was reversed in the EPA-pretreated group. The two receptors of ET system, ET_A and ET_B, tended to be increased in the ET-1–treated group, but no statistical significance was seen among study groups. Endothelin-1 increased prepro–ET-1 and ECE-1 mRNA expression in hypertrophied-neonatal cardiomyocytes, and this was reversed with EPA pretreatment. Thus, EPA may play a crucial role in the regression of ET-1–induced cardiomyocyte hypertrophy, partly through the suppression of ET-1 and ECE-1 expression.

Get full access to this article

View all access options for this article.

References

Chien KR, Zhu H, Knowlton KU, Miller-Hance W, van-Bilsen M, O’Brien TX, Evans SM. Transcriptional regulation during cardiac growth and development. Annu Rev Physiol 55:77–95, 1993.

Irukayama-Tomobe Y, Miyauchi T, Sakai S, Kasuya Y, Ogata T, Takanashi M, Iemitsu M, Sudo T, Goto K, Yamaguchi I. Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-alpha partly via blockade of c-Jun NH2-terminal kinase pathway. Circulation 109:904–910, 2004.

Giannessi D, Del Ry S, Vitale RL. The role of endothelins and their receptors in heart failure. Pharmacol Res 43:111–126, 2001.

Yanagisawa M, Masaki T. Molecular biology and biochemistry of the endothelins. Trends Pharmacol Sci 10:374–378, 1989.

Ito H. Endothelin and cardiac hypertrophy. Life Sci 61:585–593, 1997.

Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival—4. Cardiovasc Drugs Ther 11: 485–491, 1997.

von Au D, Brandle M, Rupp H, Jacob R. Influence of a diet rich in fish oil on blood pressure, body weight and cardiac hypertrophy in spontaneously hypertensive rats. Eur J Appl Physiol Occup Physiol 58: 97–99, 1988.

Maeda S, Miyauchi T, Iemitsu M, Tanabe T, Yokota T, Goto K, Yamaguchi I, Matsuda M. Effects of exercise training on expression of endothelin-1 mRNA in the aorta of aged rats. Clin Sci 103:118S–123S, 2002.

Sakurai T, Yanagisawa M, Inoue A, Ryan US, Kimura S, Mitsui Y, Goto K, Masaki T. cDNA cloning, sequence analysis and tissue distribution of rat preproendothelin-1 mRNA. Biochem Biophys Res Commun 175:44–47, 1991.

10.

Shimada K, Takahashi M, Tanzawa K. Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem 269:18275–18278, 1994.

11.

Lin HY, Kaji EH, Winkel GK, Ives HE, Lodish HF. Cloning and functional expression of a vascular smooth muscle endothelin-1 receptor. Proc Natl Acad Sci U S A 88:3185–3189, 1991.

12.

Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a nonisopeptide-selective subtype of the endothelin receptor. Nature 348:732–735, 1990.

13.

Tso J, Sun XH, Kao TH, Reece KS, Wu R. Isolation and characterization of rat glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res 13:2485–2502, 1985.

14.

Yorikane R, Sakai S, Miyauchi T, Sakurai T, Sugishita Y, Goto K.Increased production of endothelin-1 in the hypertrophied rat heart due to pressure overload. FEBS Lett 332:31–34, 1993.

15.

Sakai S, Miyauchi T, Sakurai T, Kasuya Y, Ihara M, Yamaguchi I, Goto K, Sugishita Y. Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure: marked increase in endothelin-1 production in the failing heart. Circulation 93:1214–1222, 1996.

16.

Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, Nogami A, Murumo F, Hiroe M. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 92:398–403, 1993.

17.

Kaburagi S, Hasegawa K, Morimoto T, Araki M, Sawamura T, Masaki T, Sasayama S. The role of endothelin-converting enzyme-1 in the development of alpha1-adrenergic-stimulated hypertrophy in cultured neonatal rat cardiac myocytes. Circulation 99:292–298, 1999.

18.

Lee GR, Bell D, Kelso EJ, Argent CC, McDermott BJ. Evidence for altered ET_B receptor characteristics during development and progression of ventricular cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 287:H425–H432, 2004.

19.

Kanno K, Hirata Y, Tsujino M, Imai T, Shichiri M, Ito H, Marumo F. Up-regulation of ET_B receptor subtype mRNA by angiotensin II in rat cardiomyocytes. Biochem Biophys Res Commun 194:1282–1287, 1993.

Effect of Eicosapentaenoic Acid on the Different Endothelin System Components in Endothelin-1–Induced Hypertrophied Cardiomyocytes

Abstract

Get full access to this article

References