ECE2014 Poster Presentations Cardiovascular Endocrinology & Lipid Metabolism (41 abstracts)
Epigenetic control of renin–angiotensin–aldosterone system in hypertrophic heart
Yoshiyu Takeda , Fen Wang , Masashi Demura , Takashi Yoneda , Shigehiro Karashima , Yuan Cheng , Mitsuhiro Kometani & Masashi Ohe
Kanazawa University, Kanazawa, Japan.
The activation of local renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the overall pathophysiology of the cardiovascular diseases. We have reported increased mRNA levels of angiotensinogen, angiotensin converting enzyme (ACE) and CYP11B2 (aldosterone synthase gene) in the heart of salt-sensitive hypertensive rats complicated with cardiac hypertrophy. However, the mechanism of control of gene expression of each component of RAAS gene in the heart is unknown. We analyzed epigenomic alteration, which controls the CYP11B2 in the human heart (cardiomyopathy, n=9; non-cardiomyopathy, n=6). CpG dinucleotides in the CYP11B2 promoter were found to be hypermethylated in tissues with low expression, but not in those with high expression, of CYP11B2. Methylation of the CYP11B2 promoter fused to a reporter gene decreased transcriptional activity. CYP11B2 mRNA levels were inversely correlated with CYP11B2 methylation in human myocardium, and increased CYP11B2 mRNA levels were associated with CYP11B2 demethylation in the hypertrophic heart. CpG dinucleotides in the angiotensinogen gene promoter were also found to be hypermethylated in tissues with low expression. Hypertrophic hearts induced by high salt intake showed hypomethylated state of angiotensinogen gene. Advances in understanding of epigenetic modifications of tissue RAAS in the progression of cardiac hypertrophy and heart failure could be of great significance in predicting the pace of disease progression, developing targeted therapeutic strategies in preventing the progression of cardiovascular diseases.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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