Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury

Jianhai Du, Zhixin Li, Quan Zhen Li, Tongju Guan, Qiuhui Yang, Hao Xu, Kirkwood A. Pritchard, Amadou K.S. Camara, Yang Shi

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background--We reported previously that Brown Norway (BN) rats are more resistant to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To identify the unique genes differentially expressed in the hearts of these rats, we used DNA microarray analysis and observed that enoyl coenzyme A hydratase-containing domain 2 (ECHDC2) is highly expressed (≈ 18-fold) in the SS hearts compared with the BN hearts. Methods and Results--RT-PCR, Western blot, and immunohistochemistry analyses verified that ECHDC2 was highly expressed in SS hearts compared with the BN hearts. ECHDC2 gene locates at chromosome 5 of rat and is expressed in mitochondria of the heart, mainly in cardiomyocytes but not in cardiofibroblasts. Overexpression of ECHDC2 in cells increased susceptibility to I/R injury while knockdown of ECHDC2 enhanced resistance to I/R injury. Furthermore, we observed that left anterior descending coronary artery ligation-induced myocardial infarction was more severe in the SS hearts than in the BN hearts or SSBN5 hearts, which was built on SS rats but had the substitution of chromosome 5 from BN rats. We also demonstrated that ECHDC2 did not alter mitochondrial O2 consumption, metabolic intermediates and ATP production. By gas chromatography-mass spectrometry, we found that ECHDC2 overexpression increased the levels of the cellular branched chain amino acids leucine and valine. Conclusion--ECHDC2, a mitochondrial protein, may be involved in regulating cell death and myocardial injury. Its deficiency in BN rats contributes to their increased resistance to myocardial I/R compared with SS rats. ECHDC2 increases branched chain amino acid metabolism and appears to be a novel regulator linking cell metabolism with cardiovascular disease.

Original languageEnglish (US)
Article numbere000233
JournalJournal of the American Heart Association
Volume2
Issue number5
DOIs
StatePublished - Jan 1 2013

Keywords

  • Branched amino acid metabolism
  • Cell death
  • ECHDC2
  • Ischemia/reperfusion injury
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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