Effect of eicosapentaenoic acid on the different endothelin system components in endothelin-1-induced hypertrophied cardiomyocytes.
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 microM). 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.
Shimojo
Nobutake
N
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Jesmin
Subrina
S
Zaedi
Sohel
S
Soma
Masaaki
M
Kobayashi
Tsutomu
T
Maeda
Seiji
S
Yamaguchi
Iwao
I
Goto
Katsutoshi
K
Miyauchi
Takashi
T
D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D008666:Metalloendopeptidases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D019332:Endothelin-1; D012333:RNA, Messenger; D015118:Eicosapentaenoic Acid; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes