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Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury. J Am Heart Assoc 2013 Oct 09;2(5):e000233

Date

10/11/2013

Pubmed ID

24108764

Pubmed Central ID

PMC3835224

DOI

10.1161/JAHA.113.000233

Scopus ID

2-s2.0-84891718724   7 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.

Author List

Du J, Li Z, Li QZ, Guan T, Yang Q, Xu H, Pritchard KA, Camara AK, Shi Y

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Enoyl-CoA Hydratase
Hydro-Lyases
Male
Myocardial Reperfusion Injury
Rats
Rats, Inbred BN
Rats, Inbred Dahl
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a