Mitogen-activated protein kinase and natural phenolic compounds in cardiovascular remodeling

Mitogen-activated protein kinase and natural phenolic compounds in cardiovascular remodeling

Cellular responses require the activation of intracellular signal transduction pathways, particularly the activation of protein kinases. Mitogen-activated protein kinases (MAPKs) are responsible for a diverse range of physiological processes in cells including growth, survival, and apoptosis. Three different kinases, known as extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 MAPKs, are activated by dual phosphorylation on both threonine and tyrosine residues within a Thr-Xaa-Tyr motif. JNKs and p38 MAPKs trigger apoptosis whereas ERKs are responsible for cellular survival in the presence of noxious stimuli. Intracellular stress mediated via free radical generation and other proinflammatory mediators may activate the MAPKs. Impaired G-protein-coupled receptor signaling, responsible for most of the complications associated with obesity and cardiovascular disorders, activates the MAPK pathway, which ultimately activates downstream transcription factors and gene expression related to cardiac growth. Polyphenolic compounds possessing strong antioxidant and anti inflammatory properties improve stress-activated disorders such as hypertension, atherosclerosis, cardiac hypertrophy, and remodeling. This review focuses on the underlying mechanisms of cardiac remodeling in oxidative stress and the therapeutic potential of natural compounds inhibiting MAPKs.

Chapter 6. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher.