Skip Navigation

European Heart Journal 2004 25(14):1221-1229; doi:10.1016/j.ehj.2004.05.003
Copyright © 2004 by the European Society of Cardiology.
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Yamamoto, K.
Right arrow Articles by Masuyama, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamamoto, K.
Right arrow Articles by Masuyama, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Clinical research

N-Methylethanolamine attenuates cardiac fibrosis and improves diastolic function: inhibition of phospholipase D as a possible mechanism

Kazuhiro Yamamotoa,*, Yoshito Takahashib, Toshiaki Manoa,c, Yasushi Sakataa,c, Nagahiro Nishikawaa,c, Junichi Yoshidaa,c, Yuichi Oishib, Masatsugu Horia, Takeshi Miwac, Shintaro Inoueb and Tohru Masuyamaa,1

a Department of Internal Medicine and Therapeutics,Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan
b Basic Research Laboratory, Kanebo Ltd., Odawara, Japan
c Genome Information Research Center, Osaka University, Suita, Japan

* Corresponding author. Tel.: +81-6-6879-6612; fax : +81-6-6879-6613
E-mail address: kazuhiro{at}medone.med.osaka-u.ac.jp

Received 18 October 2003; revised 30 April 2004; accepted 6 May 2004

Abstract

Aim Ventricular fibrosis is promoted by many effectors that chronically activate phospholipase D (PLD), and induces cardiac dysfunction and heart failure in cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised that an administration of an analogue of ethanolamine, N-methylethanolamine (MEA), decreases PLD activity through a negative feedback mechanism, suppresses collagen accumulation, and thus prevents organ dysfunction.

Methods and results In human fibroblasts 1-butanol inhibited collagen synthesis and enhanced collagenase production, but iso-butanol did not. These indicate crucial roles of PLD in collagen synthesis and degradation. In fibroblasts, MEA dose-dependently decreased PLD activity, inhibited collagen synthesis and enhanced collagenase production. In a hypertensive heart failure model using Dahl–Iwai salt-sensitive rats, PLD activity increased with progressive ventricular fibrosis, leading to myocardial stiffening and overt heart failure. Long-term administration of MEA did not significantly decrease blood pressure, however, but decreased PLD activity and collagen content with inhibited gene expression of collagens, leading to the prevention of myocardial stiffening and haemodynamic deterioration. MEA also attenuated ventricular hypertrophy, another detrimental structural alteration.

Conclusion MEA may exert therapeutic effects on cardiac disorders due to ventricular fibrosis through suppression of PLD activity and modulation of the fibrosis pathway even without relief from mechanical stress.

Key Words: Collagen • Diastole • Heart failure


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 HypertensionHome page
S. Klotz, I. Hay, G. Zhang, M. Maurer, J. Wang, and D. Burkhoff
Development of Heart Failure in Chronic Hypertensive Dahl Rats: Focus on Heart Failure With Preserved Ejection Fraction
Hypertension, May 1, 2006; 47(5): 901 - 911.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. Yoshida, K. Yamamoto, T. Mano, Y. Sakata, M. Nishio, T. Ohtani, M. Hori, T. Miwa, and T. Masuyama
Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats
Cardiovasc Res, October 1, 2005; 68(1): 118 - 127.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.