ArticleAmerican journal of physiology. Heart and circulatory physiology2022
Sex-specific phenotypes in the aging mouse heart and consequences for chronic fibrosis.
Article in American journal of physiology. Heart and circulatory physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Assessing health in aging male and female mice: does cardiac function dictate frailty or physical resilience?The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Non-alcoholic fatty liver disease as a predictor of atrial fibrillation recurrence following ablation: a retrospective study.Cardiovascular diagnosis and therapy · 2025Article
- Camellia sinensis powder rich in epicatechin and polyphenols attenuates isoprenaline induced cardiac injury by activating the Nrf2 HO1 antioxidant pathway in rats.Scientific reports · 2025Article
- Organ fibrosis: beyond collagen I expression. Fibroblast phenotype and basement membrane proteins.American journal of physiology. Cell physiology · 2025Review
- Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Different impact of female gender on the outcome of catheter ablation between paroxysmal and persistent atrial fibrillation.BMC cardiovascular disorders · 2025Article
- Transient angiotensin-converting enzyme inhibition confers sex-specific protection against angiotensin II-induced cardiac remodeling.American journal of physiology. Cell physiology · 2025Article
- Sex Differences in Response to Diet Enriched With Glutathione Precursors in the Aging Heart.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles.Aging cell · 2025Article
- Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.Circulation. Cardiovascular imaging · 2024Article
- Sex as a biological variable for cardiovascular physiology.American journal of physiology. Heart and circulatory physiology · 2024Review
- Fibroblasts and immune cells: at the crossroad of organ inflammation and fibrosis.American journal of physiology. Heart and circulatory physiology · 2024Review
- Exploring the Impact of BKInternational journal of molecular sciences · 2024Review
- Identifying sex similarities and differences in structure and function of the sinoatrial node in the mouse heart.Frontiers in medicine · 2024Article
- Fibroblasts under pressure: cardiac fibroblast responses to hypertension and antihypertensive therapies.American journal of physiology. Heart and circulatory physiology · 2024Review
- Substrate stiffness modulates cardiac fibroblast activation, senescence, and proinflammatory secretory phenotype.American journal of physiology. Heart and circulatory physiology · 2024Article
- Guidelines on the use of sex and gender in cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2024Review
- A defective mechanosensing pathway affects fibroblast-to-myofibroblast transition in the old male mouse heart.iScience · 2023Article
- Sex matters in the aging heart: implications for antifibrotic therapies.American journal of physiology. Heart and circulatory physiology · 2022Article
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9 authors at 2 institutions in 2 countries.
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Abstract
The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional study over a 3-mo period. We found sex-related differences in extracellular matrix (ECM) composition as well as heart function indices at baseline, which were further accentuated by AICAR treatment. AICAR attenuated the age-related increase in left atrial volume (LAV, an indicator of diastolic dysfunction) in female but not in male hearts, which was associated with reduced collagen deposition in the old female heart, and reduced the transcription factor Gli1 expression in cardiac fibroblasts. We further demonstrated that collagen synthesis was dependent on Gli1, which is a target of AMPK-mediated degradation. By contrast, AICAR had a minor impact on cardiac fibroblasts in the old male heart because of blunted AMPK phosphorylation. Hence, it did not significantly improve old male heart function indices. In conclusion, we demonstrated that male and female hearts are phenotypically different, and sex-specific differences need to be considered when analyzing the response to pharmacological intervention.
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