Study Links Estrogen Deficiency to Diastolic Heart Dysfunction in Female Mice
A mouse study published on bioRxiv found that surgically induced estrogen deficiency significantly worsened diastolic dysfunction in hypertensive female mice without affecting ejection fraction, mimicking a severe form of heart failure with preserved ejection fraction (HFpEF). Researchers used ovariectomized mice with induced hypertension and cardiac pressure overload to model post-menopausal conditions, finding parallel mitochondrial dysfunction, increased oxidative stress, and cardiac fibrosis. The findings raise questions about whether similar estrogen-dependent mechanisms contribute to the high prevalence of HFpEF in post-menopausal women.
Researchers investigated the role of estrogen (17β-estradiol, E2) deficiency in diastolic dysfunction (DD), a form of heart failure with preserved ejection fraction (HFpEF) that disproportionately affects post-menopausal women. Female mice were subjected to hypertension and cardiac pressure overload, then subdivided to undergo ovariectomy (OVX) to simulate menopause-related estrogen loss. OVX-associated E2 deficiency progressively worsened diastolic function over 21 days without reducing ejection fraction or stroke volume, closely replicating a severe HFpEF phenotype. These functional changes were accompanied by mitochondrial dysfunction, upregulation of stress, fibrosis, and energy metabolism genes, reduced cardiomyocyte elasticity, increased reactive oxygen species production, and extracellular fibrosis. Notably, treatment with E2 or a G-protein-coupled estrogen receptor (GPER) agonist restored normal diastolic function, while estrogen receptor beta agonists did not, pointing to a specific receptor pathway. The study establishes a robust preclinical model of estrogen-deficiency-driven DD and suggests that estrogen signaling through GPER may be a mechanistically important target in post-menopausal cardiac disease.
What's missing
As a preprint, this study has not yet undergone formal peer review, and its findings should be interpreted with caution. The study is limited to a mouse model, and direct translation to post-menopausal women remains unestablished; the authors themselves note this as an open question. The study does not address long-term safety or efficacy of GPER-targeted therapies, nor does it examine whether findings differ across age groups or varying degrees of hypertension severity.
What different sources said
- bioRxivCenter
Estrogen-Deficiency Degrades Left Ventricular Diastolic Function and Energy Metabolism in Hypertensive Female Mice
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.