Research ArticleCardiology

Chronic hypoxia–induced Cirbp hypermethylation attenuates hypothermic cardioprotection via down-regulation of ubiquinone biosynthesis

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Science Translational Medicine  24 Apr 2019:
Vol. 11, Issue 489, eaat8406
DOI: 10.1126/scitranslmed.aat8406

Cardioprotection loses its cool

Hypothermia reduces a tissue’s metabolic demand and can be cardioprotective; however, some patients incur injury after cardiopulmonary bypass (CPB) performed with therapeutic hypothermia. Liu et al. studied the role of cold-inducible RNA binding protein (CIRBP), a stress-induced protein known to be neuroprotective, during CPB under normoxic and hypoxic conditions. Chronic hypoxia caused hypermethylation of the Cirbp promoter region, reducing protein expression in response to cold stress and antioxidant ubiquinone synthesis and abrogating cardioprotective effects. Supplementing ubiquinone during CPB could restore cardioprotection in rats exposed to chronic hypoxia. This study helps explain why hypothermia may not be cardioprotective in patients with chronic hypoxic conditions.

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