Research ArticleHeart Failure

Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH

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Science Translational Medicine  08 Nov 2017:
Vol. 9, Issue 415, eaam8574
DOI: 10.1126/scitranslmed.aam8574

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A fetal gene for heart failure

One way the heart responds to cardiac injury is by reverting gene expression to developmental patterns. Van der Pol et al. discovered that Oplah, a gene encoding an enzyme that converts 5-oxoproline to glutamate as part of the γ-glutamyl cycle, was repressed in adult mouse hearts with heart failure. Depleting Oplah in cardiomyocytes increased 5-oxoproline and oxidative stress, and elevated 5-oxoproline in blood samples from patients with heart failure was associated with worse outcome. Overexpressing OPLAH protected mice from cardiac injury in models of heart failure, suggesting that OPLAH and other fetal-like genes could be therapeutic targets.