ArticleThe Journal of physiology2014
Forkhead BoxO transcription factors restrain exercise-induced angiogenesis.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Biochemical neuroplasticity in the cerebellum after physical exercise: Systematic review and meta-analysis.PloS one · 2025Pooled it
- Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Trial
- The effect of regular physical activity during hemodialysis on levels of FOXO proteins and myostatin concentration.Archives of medical science : AMS · 2026Article
- The effect of acute prolonged swimming on skeletal muscle metabolism in different muscle types of rats after nine days of dexamethasone treatment.Frontiers in physiology · 2026Article
- The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.European journal of applied physiology · 2025Article
- Dietary RNA from Torula Yeast Prevents Capillary Regression in Atrophied Skeletal Muscle in Rats.Life (Basel, Switzerland) · 2024Article
- Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.ACS chemical biology · 2023Article
- Role of muscle FOXO gene in exercise against the skeletal muscle and cardiac age-related defects and mortality caused by high-salt intake in Drosophila.Genes & nutrition · 2023Article
- Angiostatic freeze or angiogenic move? Acute cold stress prevents angiokine secretion from murine myotubes but primes primary endothelial cells for greater migratory capacity.Frontiers in physiology · 2022Article
- Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story.Frontiers in physiology · 2021Review
- Review
- Protective effects of Brazilian propolis supplementation on capillary regression in the soleus muscle of hindlimb-unloaded rats.The journal of physiological sciences : JPS · 2019Article
- Application of transcutaneous carbon dioxide improves capillary regression of skeletal muscle in hyperglycemia.The journal of physiological sciences : JPS · 2019Article
- The role of mitochondria in angiogenesis.Molecular biology reports · 2019Review
- FOXOs in cancer immunity: Knowns and unknowns.Seminars in cancer biology · 2018Review
- Metabolic Regulation of Angiogenesis in Diabetes and Aging.Physiology (Bethesda, Md.) · 2017Review
- The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise.The Journal of biological chemistry · 2016Article
- Physiological Capillary Regression is not Dependent on Reducing VEGF Expression.Microcirculation (New York, N.Y. : 1994) · 2016Review
- Advances and challenges in skeletal muscle angiogenesis.American journal of physiology. Heart and circulatory physiology · 2016Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The physiological process of exercise-induced angiogenesis involves the orchestrated upregulation of angiogenic factors together with repression of angiostatic factors. The Forkhead Box 'O' (FoxO) transcription factors promote an angiostatic environment in pathological contexts. We hypothesized that endothelial FoxO1 and FoxO3a also play an integral role in restricting the angiogenic response to aerobic exercise training. A single exercise bout significantly increased levels of FoxO1 and FoxO3a mRNA (5.5- and 1.7-fold, respectively) and protein (1.7- and 2.2-fold, respectively) within the muscles of mice 2 h post-exercise compared to sedentary. Training abolished the exercise-induced increases in both FoxO1 and FoxO3a mRNA and proteins, and resulted in significantly lower nuclear levels of FoxO1 and FoxO3a protein (0.5- and 0.4-fold, respectively, relative to sedentary). Thrombospondin 1 (THBS1) protein level closely mirrored the expression pattern of FoxO proteins. The 1.7-fold increase in THBS1 protein following acute exercise no longer occurred after 10 days of repeated exercise. Endothelial cell-directed conditional deletion of FoxO1/3a/4 in mice prevented the increase in THBS1 mRNA following a single exercise bout. Mice harbouring the endothelial FoxO deletion also demonstrated a significant 20% increase in capillary to muscle fibre ratio after only 7 days of training while 14 days of training was required to elicit a similar increase in wildtype littermates. Our results demonstrate that the downregulation of FoxO1 and FoxO3a proteins facilitates angiogenesis in response to repeated exercise. In conclusion, FoxO proteins can delay exercise-induced angiogenesis, and thus are critical regulators of the physiological angiogenic response in skeletal muscle.
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