Quick Search:

is currently disabled due to reindexing of the ZORA database. Please use Advanced Search.
uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-23358

Krishnan, J; Suter, M; Windak, R; Krebs, T; Felley, A; Montessuit, C; Tokarska-Schlattner, M; Aasum, E; Bogdanova, A; Perriard, E; Perriard, J C; Larsen, T; Pedrazzini, T; Krek, W (2009). Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metabolism, 9(6):512-524.

[img] PDF - Registered users only
2MB

Abstract

Development of cardiac hypertrophy and progression to heart failure entails profound changes in myocardial metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation. We report that hypoxia-inducible factor (HIF)1alpha and PPARgamma, key mediators of glycolysis and lipid anabolism, respectively, are jointly upregulated in hypertrophic cardiomyopathy and cooperate to mediate key changes in cardiac metabolism. In response to pathologic stress, HIF1alpha activates glycolytic genes and PPARgamma, whose product, in turn, activates fatty acid uptake and glycerolipid biosynthesis genes. These changes result in increased glycolytic flux and glucose-to-lipid conversion via the glycerol-3-phosphate pathway, apoptosis, and contractile dysfunction. Ventricular deletion of Hif1alpha in mice prevents hypertrophy-induced PPARgamma activation, the consequent metabolic reprogramming, and contractile dysfunction. We propose a model in which activation of the HIF1alpha-PPARgamma axis by pathologic stress underlies key changes in cell metabolism that are characteristic of and contribute to common forms of heart disease.

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
DDC:570 Life sciences; biology
Language:English
Date:2009
Deposited On:21 Oct 2009 07:09
Last Modified:27 Nov 2013 17:15
Publisher:Elsevier
ISSN:1550-4131
Publisher DOI:10.1016/j.cmet.2009.05.005
PubMed ID:19490906
Citations:Web of Science®. Times Cited: 76
Google Scholar™
Scopus®. Citation Count: 79

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page