ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Murine double minute-2 expression is required for capillary maintenance and exercise-induced angiogenesis in skeletal muscle.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Endurance training increases a ubiquitylated form of histone H3 in the skeletal muscle, supporting Notch1 upregulation in an MDM2-dependent manner.The Journal of physiology · 2025Article
- Heterogenous circulating miRNA changes in ME/CFS converge on a unified cluster of target genes: A computational analysis.PloS one · 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
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- Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story.Frontiers in physiology · 2021Review
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- 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
- Considering the Role of Murine Double Minute 2 in the Cardiovascular System?Frontiers in cell and developmental biology · 2019Review
- 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
- Endurance training induces fiber type-specific revascularization in hindlimb skeletal muscles of rats with chronic heart failure.Iranian journal of basic medical sciences · 2017Article
- Physiological Capillary Regression is not Dependent on Reducing VEGF Expression.Microcirculation (New York, N.Y. : 1994) · 2016Review
- (-)-Epicatechin combined with 8 weeks of treadmill exercise is associated with increased angiogenic and mitochondrial signaling in mice.Frontiers in pharmacology · 2015Article
- Forkhead BoxO transcription factors restrain exercise-induced angiogenesis.The Journal of physiology · 2014Article
- Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.PloS one · 2014Article
- Endothelial FoxO1 is an intrinsic regulator of thrombospondin 1 expression that restrains angiogenesis in ischemic muscle.Angiogenesis · 2013Article
- Novel perspective: exercise training stimulus triggers the expression of the oncoprotein human double minute-2 in human skeletal muscle.Physiological reports · 2013Article
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/Δ7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/Δ7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/Δ7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wild-type muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/Δ7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle.
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