ArticleJournal of the American Heart Association2021
Cardiac Fibroblasts Mediate a Sexually Dimorphic Fibrotic Response to β-Adrenergic Stimulation.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Isoproterenol Induces Cardiac Injury and Senescence in Sprague-Dawley Rats: A Cost-Effective Pharmacological Model.Biomedicines · 2026Article
- Exploring sex differences in myocardial fibrosis in patients with structurally normal hearts.Scientific reports · 2025Article
- β2-Adrenergic receptor regulates osteoblast differentiation and migration and C-terminal β-catenin phosphorylation.Biochemical and biophysical research communications · 2025Article
- Signals from the extracellular matrix: Region- and sex-specificity in cardiac aging.Current opinion in cell biology · 2025Review
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Transient angiotensin-converting enzyme inhibition confers sex-specific protection against angiotensin II-induced cardiac remodeling.American journal of physiology. Cell physiology · 2025Article
- Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals.Animal models and experimental medicine · 2025Review
- Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.Osteoarthritis and cartilage · 2024Article
- Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling.Clinical and translational medicine · 2024Article
- Hearts apart: sex differences in cardiac remodeling in health and disease.The Journal of clinical investigation · 2024Review
- Fibroblasts under pressure: cardiac fibroblast responses to hypertension and antihypertensive therapies.American journal of physiology. Heart and circulatory physiology · 2024Review
- Juvenile physical activity protects against isoproterenol-induced cardiac dysfunction later in life.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- More than just a small left ventricle: the right ventricular fibroblast and ECM in health and disease.American journal of physiology. Heart and circulatory physiology · 2023Review
- Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Postmenopausal Women.JACC. Advances · 2023Article
- Exposure to Doxorubicin Modulates the Cardiac Response to Isoproterenol in Male and Female Mice.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Periodontal Disease Associated With Interstitial Myocardial Fibrosis: The Multiethnic Study of Atherosclerosis.Journal of the American Heart Association · 2023Article
- A role for misaligned gene expression of fetal gene program in the loss of female-specific cardiovascular protection in young obese and diabetic females.Frontiers in endocrinology · 2023Review
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- Regression from pathological hypertrophy in mice is sexually dimorphic and stimulus specific.American journal of physiology. Heart and circulatory physiology · 2022Article
- Trimetazidine Reduces Cardiac Fibrosis in Rats by Inhibiting NOX2-Mediated Endothelial-to-Mesenchymal Transition.Drug design, development and therapy · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Background Biological sex is an important modifier of cardiovascular disease and women generally have better outcomes compared with men. However, the contribution of cardiac fibroblasts (CFs) to this sexual dimorphism is relatively unexplored. Methods and Results Isoproterenol (ISO) was administered to rats as a model for chronic β-adrenergic receptor (β-AR)-mediated cardiovascular disease. ISO-treated males had higher mortality than females and also developed fibrosis whereas females did not. Gonadectomy did not abrogate this sex difference. To determine the cellular contribution to this phenotype, CFs were studied. CFs from both sexes had increased proliferation in vivo in response to ISO, but CFs from female hearts proliferated more than male cells. In addition, male CFs were significantly more activated to myofibroblasts by ISO. To investigate potential regulatory mechanisms for the sexually dimorphic fibrotic response, β-AR mRNA and PKA (protein kinase A) activity were measured. In response to ISO treatment, male CFs increased expression of β1- and β2-ARs, whereas expression of both receptors decreased in female CFs. Moreover, ISO-treated male CFs had higher PKA activity relative to vehicle controls, whereas ISO did not activate PKA in female CFs. Conclusions Chronic in vivo β-AR stimulation causes fibrosis in male but not female rat hearts. Male CFs are more activated than female CFs, consistent with elevated fibrosis in male rat hearts and may be caused by higher β-AR expression and PKA activation in male CFs. Taken together, our data suggest that CFs play a substantial role in mediating sex differences observed after cardiac injury.
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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 Socratic graph.