Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia.

ABSTRACT: Since impaired mitochondrial ATP production in cardiomyocytes is thought to lead to heart failure, a drug that protects mitochondria and improves ATP production under disease conditions would be an attractive treatment option. In this study, we identified small-molecule drugs, including the anti-parasitic agent, ivermectin, that maintain mitochondrial ATP levels under hypoxia in cardiomyocytes. Mechanistically, transcriptomic analysis and gene silencing experiments revealed that ivermectin increased mitochondrial ATP production by inducing Cox6a2, a subunit of the mitochondrial respiratory chain. Furthermore, ivermectin inhibited the hypertrophic response of human induced pluripotent stem cell-derived cardiomyocytes. Pharmacological inhibition of importin β, one of the targets of ivermecti

SUBMITTER: Nagai H 

PROVIDER: S-EPMC5652136 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature