HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Integrated proteomic and metabolomic analysis reveals the NADH-mediated TCA cycle and energy metabolism disorders based on a new model of chronic progressive heart failure.

AbstractBACKGROUND:
Despite major advances in the treatment of heart failure (HF), it remains the major cause of mortality and morbidity worldwide. Experimental models of HF typically utilize acute myocardial infarction. However, the majority of clinical HFs occur gradually by a chronic progressive mechanism. Thus, more relevant models are required to aid identification, quantification, and characterization of HF, and its underlying mechanisms.
METHODS AND FINDINGS:
We developed a model of progressive chronic heart failure (CHF) in the mini-swine by placement of an ameroid constrictor on the left anterior descending coronary artery (LAD). This model demonstrated a steady decline in the cardiac function from 8 to 12 weeks, with a 50% reduction in the ejection fraction. Further, the proteomic, metabolomic and bioinformatic analyses of ischemic tissue and plasma revealed a significant alteration of the mitochondrial respiratory chain mediated by nicotinamide adenine dinucleotide (NADH), which resulted in down-regulation of malate dehydrogenase (MDH) and insufficient energy supply to support cardiac contractility and relaxation. Furthermore, significant changes in apolipoprotein A-I, low density lipoprotein (LDL), and very LDL (VLDL) in plasma indicated that lipid metabolism disorders occurred in mini-swines with myocardial ischemia via glycerolipid metabolism.
CONCLUSIONS:
We describe a stable and easily reproducible CHF model using an ameroid constrictor placed on the LAD. We found that the NADH-mediated tricarboxylic acid cycle and energy metabolism disorders are key pathophysiological mechanisms underlying CHF. These data will provide potential biomarkers for monitoring the therapeutic intervention of CHF.
AuthorsYong Wang, Chun Li, Wenjing Chuo, Zhongyang Liu, Yulin Ouyang, Dong Li, Jing Han, Yan Wu, Shuzhen Guo, Wei Wang
JournalMolecular bioSystems (Mol Biosyst) Vol. 9 Issue 12 Pg. 3135-45 (Dec 2013) ISSN: 1742-2051 [Electronic] England
PMID24108264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • NAD
  • Malate Dehydrogenase
  • NADH Dehydrogenase
Topics
  • Animals
  • Citric Acid Cycle
  • Disease Models, Animal
  • Energy Metabolism
  • Gene Expression Regulation
  • Heart Failure (blood, pathology)
  • Humans
  • Malate Dehydrogenase (metabolism)
  • Metabolomics
  • Myocardial Ischemia (blood, pathology)
  • NAD (metabolism)
  • NADH Dehydrogenase (metabolism)
  • Proteomics
  • Swine
  • Swine, Miniature

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: