MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

Abstract

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening.

• Authors: Rogério Faustino Ribeiro Junior, Erinne Rose Dabkowski, Kadambari Chandra Shekar, Kelly A O Connell, Peter A Hecker, Michael P Murphy
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 117 Pg. 18-29 (03 2018) ISSN: 1873-4596 [Electronic] United States
• PMID: 29421236 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Inc.

Chemical References

• Antioxidants
• Organophosphorus Compounds
• Ubiquinone
• mitoquinone

Topics

• Animals
• Antioxidants (pharmacology)
• Disease Models, Animal
• Heart Failure (physiopathology)
• Mitochondria (drug effects)
• Mitochondria, Heart (drug effects)
• Organophosphorus Compounds (pharmacology)
• Rats
• Ubiquinone (analogs & derivatives, pharmacology)