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

6 Citations (Scopus)

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 - 2013

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Hydro-Lyases
Coenzymes
Coenzyme A
Myocardial Ischemia
Wounds and Injuries
Norway
Reperfusion Injury
Branched Chain Amino Acids
Chromosomes, Human, Pair 5
Myocardial Reperfusion Injury
Heart Mitochondria
Myocardial Reperfusion
Mitochondrial Proteins
Valine
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Cardiac Myocytes
Leucine
Gas Chromatography-Mass Spectrometry
Genes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury. / Du, Jianhai; Li, Zhixin; Li, Quan Zhen; Guan, Tongju; Yang, Qiuhui; Xu, Hao; Pritchard, Kirkwood A.; Camara, Amadou K.S.; Shi, Yang.

In: Journal of the American Heart Association, Vol. 2, No. 5, e000233, 2013.

Research output: Contribution to journalArticle

Du, Jianhai ; Li, Zhixin ; Li, Quan Zhen ; Guan, Tongju ; Yang, Qiuhui ; Xu, Hao ; Pritchard, Kirkwood A. ; Camara, Amadou K.S. ; Shi, Yang. / Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury. In: Journal of the American Heart Association. 2013 ; Vol. 2, No. 5.
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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.",
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T1 - Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury

AU - Du, Jianhai

AU - Li, Zhixin

AU - Li, Quan Zhen

AU - Guan, Tongju

AU - Yang, Qiuhui

AU - Xu, Hao

AU - Pritchard, Kirkwood A.

AU - Camara, Amadou K.S.

AU - Shi, Yang

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Branched amino acid metabolism

KW - Cell death

KW - ECHDC2

KW - Ischemia/reperfusion injury

KW - Myocardial infarction

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