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

Journal of the American Heart Association 2013 Oct 09

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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. 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. 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.

Citation

Jianhai Du, Zhixin Li, Quan-Zhen Li, Tongju Guan, Qiuhui Yang, Hao Xu, Kirkwood A Pritchard, Amadou K S Camara, Yang Shi. Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury. Journal of the American Heart Association. 2013 Oct 09;2(5):e000233