In neurological disease and diabetes, the unfolded protein response (UPR) has been investigated for years, while its function in heart disease is less well understood. All three branches of the UPR are involved in ischaemia/reperfusion and can either protect or impair heart function. Recently, UPR has been found to play a role in arrhythmogenesis during human heart failure, and blocking UPR has an antiarrhythmic effect. This review will discuss the rationale for and challenges to targeting UPR in heart disease.
Bibliographical noteFunding Information:
The authors were supported by National Institutes of Health (NIH) Grants RO1 HL104025 (SCD), HL106592 (SCD), and a Veterans Affairs MERIT grant BX000859 (SCD). Dudley is an inventor on the following patent applications 1) PCT/US2012/020564. Scn5a splice variants for use in methods relating to sudden cardiac death and need for implanted cardiac defibrillations and 2) PCT/US2010/ 034271, drug targets for prevention of arrhythmia in heart disease. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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