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

European Heart Journal
Kazuhiro YamamotoTohru Masuyama

Abstract

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. 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 atten...Continue Reading

Citations

Aug 22, 2008·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shinji HasegawaJun Hatazawa
Apr 15, 2014·Digestive Diseases and Sciences·Xinyan ZhuWenzhuo Yang
Dec 17, 2004·Journal of Cellular and Molecular Medicine·Melissa R DentParamjit S Tappia
Aug 22, 2006·Biochemical and Biophysical Research Communications·Kenji OhguchiYoshinori Nozawa
Jul 11, 2009·Organic & Biomolecular Chemistry·Daniel R RamosJ Arturo Santaballa
May 1, 2015·Journal of Lipid Research·Rochelle K Nelson, Michael A Frohman

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