ArticleNature communications2022
Sex differences in heart mitochondria regulate diastolic dysfunction.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 109 citations in OpenAlex.
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- Epithelial QKI Protects Against Emphysema by Maintaining Mitochondrial Integrity.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell Analysis of Human Heart Failure With Preserved Ejection Fraction.Circulation research · 2026Article
- A large-scale multi-ancestry mitochondrial variant association analysis for cardiometabolic traits.Nature communications · 2026Article
- Normal reference values and determinants of right heart strain derived from speckle tracking echocardiography: a systematic review and meta-analysis.Quantitative imaging in medicine and surgery · 2026Article
- Mitochondrial Haplogroups and Left Ventricular Diastolic Dysfunction in People Living With and Without HIV.The Journal of infectious diseases · 2026Article
- Cardiac Mitochondrial Dysfunction Following Bleomycin-Induced Acute Lung Injury in Rats.bioRxiv : the preprint server for biology · 2026Article
- Demonstration of beat-to-beat, on-demand ATP synthesis in ventricular myocytes reveals sex-specific mitochondrial and cytosolic dynamics.The Journal of physiology · 2026Article
- Optimized murine HFpEF models for translational preclinical studies.ESC heart failure · 2026Article
- Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation.bioRxiv : the preprint server for biology · 2026Article
- Antenatal betamethasone impairs markers of cardiac development and function in near-term lambs.Experimental physiology · 2026Article
- Incidence and sex-related risk factors of linezolid-associated adverse drug reactions identified through electronic health records.Translational and clinical pharmacology · 2026Article
- In vitro sex-specific function-structure relationship in neonatal rat cardiac monolayers.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: etiology and sex-dependent differences.American journal of physiology. Heart and circulatory physiology · 2026Article
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- The role of mitotype variation and positive epistasis in trait differences between Saccharomyces species.Genetics · 2026Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial sex differences might underlie this bias. As part of genetic studies of heart failure in mice, we observe that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observe that expression of genes encoding mitochondrial proteins are higher in males than females in human cohorts. We test our hypothesis in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we find that mitochondrial gene expression is highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a "two-hit" mouse model of HFpEF confirm that mitochondrial function differs between sexes and is strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identify the mitochondrial gene Acsl6 as a genetic determinant of diastolic function. We validate its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.