title: Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome.
abstract: CONCLUSIONS
  Several authors have proposed a link between altered cardiac energy substrate metabolism and reactive oxygen species (ROS) generation. A cogent evidence of this association has been found in diabetic cardiomyopathy (dCM); however, experimental findings in animal models of heart failure (HF) and in human myocardium also seem to support the coexistence of the two alterations in HF.
  
  
  RESULTS
  Two important questions remain open: whether pathological changes in metabolism play an important role in enhancing oxidative stress and whether there is a common pathway linking altered substrate utilization and activation of ROS-generating enzymes, independently of the underlying cardiac pathology. In this regard, the comparison between dCM and HF is intriguing, in that these pathological conditions display very different cardiac metabolic phenotypes.
  
  
  BACKGROUND
  Our literature review on this topic indicates that a vast body of knowledge is now available documenting the relationship between the metabolism of energy substrates and ROS generation in dCM. In some cases, biochemical mechanisms have been identified. On the other hand, only a few and relatively recent studies have explored this phenomenon in HF and their conclusions are not consistent.
  
  
  CONCLUSIONS
  Better methods of investigation, especially in vivo, will be necessary to test whether the metabolic fate of certain substrates is causally linked to ROS production. If successful, these studies will place a new emphasis on the potential clinical relevance of metabolic modulators, which might indirectly mitigate cardiac oxidative stress in dCM, HF, and, possibly, in other pathological conditions.
authors.affiliation: 1Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Roul
authors.affiliation: 1Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.|2Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
mesh_terms: D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000378:metabolism*; D004734:Energy Metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
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