Sotagliflozin corrects myocardial phenotype, mitochondrial gene expression and oxidative stress in mice with hypertrophic cardiomyopathy.
- 1Cardiovascular Medicine Section, Myocardial Biology Unit, and the Clinical and Translational Institute, Boston University School of Medicine, Boston, MA, United States of America.
Abstract
Background
Hypertrophic cardiomyopathy (HCM) is associated with mitochondrial dysfunction and oxidative stress.Objective
Our goal was to determine the effects of the dual Sodium-Glucose-Linked-Transporter (SGLT) 1 and 2 inhibitor sotagliflozin (SOTA) on myocardial remodeling, diastolic function, mitochondrial gene expression and oxidative stress in mice with HCM due to the tropomyosin E180G mutation (E180G).Methods
E180G and non-carrier (NC) mice 7-8 weeks old were randomized to SOTA formulated in the chow (30 mg/kg chow) or control diet (CD) for 8 weeks. Cardiac structure and function were assessed by echocardiography at baseline, and after 4 and 8 weeks of treatment. At 8 weeks mice were sacrificed to assess myocardial histology, RNA expression and oxidative stress.Results
At baseline E180G mice had myocardial hypertrophy and diastolic dysfunction that worsened over the next 8 weeks. In E180G mice, treatment with SOTA for 8 weeks prevented further LV hypertrophy, decreased interstitial fibrosis, normalized diastolic function and decreased atrial size. In E180G hearts mitochondrial gene sets were downregulated and oxidative stress was increased. SOTA treatment upregulated mitochondrial gene sets and prevented the increase in oxidative stress. Upregulated fibrosis gene sets in E180G hearts were not affected by SOTA.Conclusions
In a mouse model of HCM, SOTA exerts beneficial effects on myocardial structure and diastolic function which are associated with restoration of down-regulated mitochondrial gene programs and correction of oxidative stress. SOTA may be of clinical value in the treatment of patients with HCM.
Related
- Hypertrophic obstructive cardiomyopathy complicated by severe midventricular obstruction treated with percutaneous transluminal septal myocardial ablation using simultaneous contrast imaging with left ventriculography and coronary angiography: a case report
- Atrial and ventricular mechanical dysfunction and myocardial injury predict long-term outcomes in hypertrophic cardiomyopathy: a retrospective cohort study
- Myocardial bridge impacts septal radiofrequency ablation safety in hypertrophic obstructive cardiomyopathy
- Body Mass Index, Valsartan, and Myocardial Remodeling in Early‐Stage Hypertrophic Cardiomyopathy: A Secondary Analysis of the Randomized VANISH Trial
- A late bloom at the apex: development of apical hypertrophic cardiomyopathy phenotype in advanced age
BibTeX
@article{qin2026sotagliflozin,
title = {{Sotagliflozin corrects myocardial phenotype, mitochondrial gene expression and oxidative stress in mice with hypertrophic cardiomyopathy.}},
author = {Fuzhong Qin and David R Pimentel and Tomas Baka and Dominique Croteau and Richard A Cohen and Ivan Luptak and Wilson S Colucci},
journal = {Journal of molecular and cellular cardiology plus},
year = {2026},
month = oct,
doi = {10.1016/j.jmccpl.2026.100873},
url = {https://europepmc.org/article/MED/42926889},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sotagliflozin corrects myocardial phenotype, mitochondrial gene expression and oxidative stress in mice with hypertrophic cardiomyopathy.
AU - Fuzhong Qin
AU - David R Pimentel
AU - Tomas Baka
AU - Dominique Croteau
AU - Richard A Cohen
AU - Ivan Luptak
AU - Wilson S Colucci
PY - 2026
DA - 2026/10/12
JO - Journal of molecular and cellular cardiology plus
DO - 10.1016/j.jmccpl.2026.100873
UR - https://europepmc.org/article/MED/42926889
AB - Background Hypertrophic cardiomyopathy (HCM) is associated with mitochondrial dysfunction and oxidative stress.Objective Our goal was to determine the effects of the dual Sodium-Glucose-Linked-Transporter (SGLT) 1 and 2 inhibitor sotagliflozin (SOTA) on myocardial remodeling, diastolic function, mitochondrial gene expression and oxidative stress in mice with HCM due to the tropomyosin E180G mutation (E180G).Methods E180G and non-carrier (NC) mice 7-8 weeks old were randomized to SOTA formulated in the chow (30 mg/kg chow) or control diet (CD) for 8 weeks. Cardiac structure and function were assessed by echocardiography at baseline, and after 4 and 8 weeks of treatment. At 8 weeks mice were sacrificed to assess myocardial histology, RNA expression and oxidative stress.Results At baseline E180G mice had myocardial hypertrophy and diastolic dysfunction that worsened over the next 8 weeks. In E180G mice, treatment with SOTA for 8 weeks prevented further LV hypertrophy, decreased interstitial fibrosis, normalized diastolic function and decreased atrial size. In E180G hearts mitochondrial gene sets were downregulated and oxidative stress was increased. SOTA treatment upregulated mitochondrial gene sets and prevented the increase in oxidative stress. Upregulated fibrosis gene sets in E180G hearts were not affected by SOTA.Conclusions In a mouse model of HCM, SOTA exerts beneficial effects on myocardial structure and diastolic function which are associated with restoration of down-regulated mitochondrial gene programs and correction of oxidative stress. SOTA may be of clinical value in the treatment of patients with HCM.
SN - 2772-9761
ER -