Elamipretide Improves Mitochondrial Function in the Failing Human Heart

JACC Basic Transl Sci. 2019 Apr 29;4(2):147-157. doi: 10.1016/j.jacbts.2018.12.005. eCollection 2019 Apr.


Negative alterations of mitochondria are known to occur in heart failure (HF). This study investigated the novel mitochondrial-targeted therapeutic agent elamipretide on mitochondrial and supercomplex function in failing human hearts ex vivo. Freshly explanted failing and nonfailing ventricular tissue from children and adults was treated with elamipretide. Mitochondrial oxygen flux, complex (C) I and CIV activities, and in-gel activity of supercomplex assembly were measured. Mitochondrial function was impaired in the failing human heart, and mitochondrial oxygen flux, CI and CIV activities, and supercomplex-associated CIV activity significantly improved in response to elamipretide treatment. Elamipretide significantly improved failing human mitochondrial function.

Keywords: ADP, adenosine diphosphate; BN-PAGE, blue native polyacrylamide gel electrophoresis; C, mitochondrial respiratory complex; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone; HF, heart failure; RCR, respiratory control ratio; SC CCF, supercomplex coupling control factor; heart failure; high-resolution respirometry; mitochondrial-targeted compounds; supercomplex.