Original ArticleEvaluation of coenzyme Q10 (CoQ10) deficiency and therapy in mouse models of cardiomyopathyPu, Tian-Tian MB, M.Med1; Wu, Wei MB1; Liang, Pei-Da MB2; Du, Jin-Chan MB1; Han, Sheng-Li M.Med, PhD2; Deng, Xiu-Ling MB, PhD1; Du, Xiao-Jun MB, PhD1,# Author Information 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xian Jiaotong University, Xi’an, China 2School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, China. #Correspondence. Phone: +61-0413174241, E-mail: [email protected]. Conflict of interest declaration: The authors declare no conflict of interest. Journal of Cardiovascular Pharmacology ():10.1097/FJC.0000000000001401, January 20, 2023. | DOI: 10.1097/FJC.0000000000001401 Buy PAP Metrics Abstract Mitochondrial dysfunction plays a key role in the development of heart failure, but targeted therapeutic interventions remain elusive. Previous studies have shown coenzyme Q10 (CoQ10) insufficiency in patients with heart disease with undefined mechanism, and modest effectiveness of CoQ10 supplement therapy. Using two transgenic mouse models of cardiomyopathy owing to cardiac overexpression of Mst1 (Mst1-TG) or β2-adrenoceptor (β2AR-TG), we studied changes in cardiac CoQ10 content and alterations in CoQ10 biosynthesis genes. We also studied in Mst1-TG mice effects of CoQ10, delivered by oral or injection regimens, on both cardiac CoQ10 content and cardiomyopathy phenotypes. HPLC and RNA-sequencing revealed in both models significant reduction in cardiac content of CoQ10 and downregulation of majority of genes encoding CoQ10 biosynthesis enzymes. Mst1-TG mice with 70% reduction in cardiac CoQ10 were treated with CoQ10 either by oral gavage or i.p. injection for 4-8 weeks. Oral regimens failed in increasing cardiac CoQ10 content, whereas injection regimen effectively restored cardiac CoQ10 level in a time-dependent manner. However, CoQ10 restoration in Mst1-TG mice did not correct mitochondrial dysfunction measured by energy metabolism, downregulated expression of marker proteins and oxidative stress, nor to preserve cardiac contractile function. In conclusion, mouse models of cardiomyopathy exhibited myocardial CoQ10 deficiency likely due to suppressed endogenous synthesis of CoQ10. In contrast to ineffectiveness of oral administration, CoQ10 administration by injection regimen in cardiomyopathy mice restored cardiac CoQ10 content, which, however, failed in achieving detectable efficacy at molecular and global functional levels. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.