%0 Journal Article %1 nagai2017antihypertrophic %A Nagai, Hiroaki %A Satomi, Tomoko %A Abiru, Akiko %A Miyamoto, Kazumasa %A Nagasawa, Koji %A Maruyama, Minoru %A Yamamoto, Satoshi %A Kikuchi, Kuniko %A Fuse, Hiromitsu %A Noda, Masakuni %A Tsujihata, Yoshiyuki %D 2017 %J The Lancet - Infectious Diseases %K cardiac ivermectin mitochondria %P 147-158 %R https://doi.org/10.1016/j.ebiom.2017.09.022 %T Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia %U https://www.thelancet.com/article/S2352-3964(17)30376-6/fulltext %V 24 %X nce 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 ivermectin, exhibited protection against mitochondrial ATP decline and cardiomyocyte hypertrophy. These findings indicate that maintaining mitochondrial ATP under hypoxia may prevent hypertrophy and improve cardiac function, providing therapeutic options for mitochondrial dysfunction.

@article{nagai2017antihypertrophic, abstract = {nce 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 ivermectin, exhibited protection against mitochondrial ATP decline and cardiomyocyte hypertrophy. These findings indicate that maintaining mitochondrial ATP under hypoxia may prevent hypertrophy and improve cardiac function, providing therapeutic options for mitochondrial dysfunction.}, added-at = {2021-08-17T18:47:39.000+0200}, author = {Nagai, Hiroaki and Satomi, Tomoko and Abiru, Akiko and Miyamoto, Kazumasa and Nagasawa, Koji and Maruyama, Minoru and Yamamoto, Satoshi and Kikuchi, Kuniko and Fuse, Hiromitsu and Noda, Masakuni and Tsujihata, Yoshiyuki}, biburl = {https://www.bibsonomy.org/bibtex/2ced14d09d73c1bbfc5966f42fa2c7564/bellao}, doi = {https://doi.org/10.1016/j.ebiom.2017.09.022}, interhash = {a5f30787836c9fe64e3c6afab431fe89}, intrahash = {ced14d09d73c1bbfc5966f42fa2c7564}, journal = {The Lancet - Infectious Diseases }, keywords = {cardiac ivermectin mitochondria}, month = {Sept }, pages = {147-158}, timestamp = {2022-04-24T11:10:50.000+0200}, title = {Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia}, url = {https://www.thelancet.com/article/S2352-3964(17)30376-6/fulltext}, volume = 24, year = {2017 } }