Sex-specific response to A1BG loss results in female dilated cardiomyopathy
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| Publicado en: | Biology of Sex Differences vol. 16 (2025), p. 1 |
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| Otros Autores: | , |
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Springer Nature B.V.
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| Acceso en línea: | Citation/Abstract Full Text Full Text - PDF |
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| 001 | 3201563113 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2042-6410 | ||
| 024 | 7 | |a 10.1186/s13293-025-00713-8 |2 doi | |
| 035 | |a 3201563113 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 264943 |2 nlm | ||
| 100 | 1 | |a Emerson, James I | |
| 245 | 1 | |a Sex-specific response to A1BG loss results in female dilated cardiomyopathy | |
| 260 | |b Springer Nature B.V. |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a BackgroundCardiac disease often manifests with sex-specific differences in frequency, pathology, and progression. However, the molecular mechanisms underlying these differences remain incompletely understood. The glycoprotein A1BG has emerged as a female-specific regulator of cardiac structure and integrity, yet its precise role in the female heart is not well characterized.MethodsTo investigate the sex-specific role of A1BG in the heart, we generated both a conditional A1bg knockout allele and an A1bg Rosa26 knockin allele. We employed histological analysis, electrocardiography, RNA sequencing (RNA-seq), transmission electron microscopy (TEM), western blotting, mass spectrometry, and immunohistochemistry to assess structural, functional, and molecular phenotypes.ResultsLoss of A1BG in cardiomyocytes leads to persistent structural remodeling in female, but not male, hearts. Despite preserved systolic function in female A1bgCM/CM mice left ventricular dilation and wall thinning are evident and sustained over time, consistent with early-stage dilated cardiomyopathy (DCM). Transcriptomic analyses reveal that A1BG regulates key metabolic pathways in females, including glucose-6-phosphate and acetyl-CoA metabolism. TEM imaging highlights sex-specific disruption of intercalated disc architecture in female cardiomyocytes. These findings suggest that the absence of A1BG initiates chronic pathological remodeling in female hearts, potentially predisposing them to DCM under stress or aging.ConclusionA1BG is essential for maintaining ventricular structural integrity in female, but not male, hearts, leading to a chronic remodeling consistent with early-stage DCM. | |
| 653 | |a Gender differences | ||
| 653 | |a Womens health | ||
| 653 | |a Glucose metabolism | ||
| 653 | |a Sex | ||
| 653 | |a Mutation | ||
| 653 | |a Heart diseases | ||
| 653 | |a Heart failure | ||
| 653 | |a Phenotypes | ||
| 653 | |a Alleles | ||
| 653 | |a Cardiomyopathy | ||
| 653 | |a Molecular modelling | ||
| 653 | |a EKG | ||
| 653 | |a Metabolism | ||
| 653 | |a Transcriptomics | ||
| 653 | |a Dilated cardiomyopathy | ||
| 653 | |a Laboratory animals | ||
| 653 | |a Proteins | ||
| 653 | |a Cardiac arrhythmia | ||
| 653 | |a Metabolic pathways | ||
| 653 | |a Cardiomyocytes | ||
| 653 | |a Cloning | ||
| 653 | |a Microscopy | ||
| 653 | |a Cardiovascular disease | ||
| 653 | |a Females | ||
| 653 | |a Immunohistochemistry | ||
| 653 | |a Transmission electron microscopy | ||
| 653 | |a Mass spectroscopy | ||
| 653 | |a Structure-function relationships | ||
| 653 | |a Ventricle | ||
| 653 | |a Albinism | ||
| 653 | |a Cardiac function | ||
| 653 | |a Males | ||
| 653 | |a Coronary artery disease | ||
| 653 | |a Western blotting | ||
| 700 | 1 | |a Shi, Wei | |
| 700 | 1 | |a Conlon, Frank L | |
| 773 | 0 | |t Biology of Sex Differences |g vol. 16 (2025), p. 1 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3201563113/abstract/embedded/75I98GEZK8WCJMPQ?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3201563113/fulltext/embedded/75I98GEZK8WCJMPQ?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3201563113/fulltextPDF/embedded/75I98GEZK8WCJMPQ?source=fedsrch |