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N-methylethanolamine attenuates cardiac fibrosis and improves diastolic function: inhibition of phospholipase D as a possible mechanism.
- Source :
-
European heart journal [Eur Heart J] 2004 Jul; Vol. 25 (14), pp. 1221-9. - Publication Year :
- 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.<br />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.<br />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.
- Subjects :
- Animals
Blood Pressure physiology
Collagenases drug effects
Collagenases metabolism
Enzyme Inhibitors therapeutic use
Ethanolamines therapeutic use
Fibroblasts drug effects
Fibroblasts metabolism
Fibrosis enzymology
Fibrosis prevention & control
Heart Ventricles enzymology
Heart Ventricles pathology
Male
Phospholipase D drug effects
Rats
Rats, Inbred Dahl
Ventricular Dysfunction enzymology
Collagen antagonists & inhibitors
Enzyme Inhibitors pharmacology
Ethanolamines pharmacology
Phospholipase D antagonists & inhibitors
Ventricular Dysfunction prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0195-668X
- Volume :
- 25
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- European heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 15246640
- Full Text :
- https://doi.org/10.1016/j.ehj.2004.05.003