Abstract
Muscle‐derived SDF‐1α/CXCL12 modulates endothelial cell proliferation but is not required for exercise training‐induced angiogenesis
The FASEB journal, Vol.33(S1), pp.lb433-lb433
04/2019
DOI: 10.1096/fasebj.2019.33.1_supplement.lb433
Abstract
Chronic elevations in contractile activity, as observed with exercise training, increase capillarity density in skeletal muscle. Here, we demonstrate that the stromal cell‐derived factor‐1 alpha (SDF‐1α/CXCL12) is the most abundantly expressed angiogenesis‐associated chemokine in capillary‐rich oxidative soleus and exercise‐trained plantaris muscles. CXCL12 is also increased in muscle‐specific peroxisome proliferator‐activated receptor γ coactivator 1α transgenic mice (PGC‐1α mTg) when compared to wild‐type littermates. Additionally, CXCL12 is increased in C2C12 myotubes by cyclic mechanical stretch. Furthermore, exposure of human umbilical vein endothelial cells (HUVEC) to conditioned medium from cyclically stretched C2C12 myotubes enhanced cell proliferation. Such an effect was specific to CXCL12 signaling because co‐treatment with AMD3100, an antagonist of the CXCL12 receptor CXCR4, disrupted the proliferative response. To gain further insight into a potential role for CXCL12 in modulating chronic contractile activity‐induced angiogenesis in vivo, we studied muscle‐specific CXCL12 knockout mice (CXCL12 mKO). Interestingly, our results demonstrate that these mice have normal baseline capillary density and preserved angiogenesis when exercise‐trained. These findings are consistent with a muscle‐derived CXCL12‐dependent modulatory role of endothelial cell proliferation in response to increased contractile activity. However, muscle‐derived CXCL12 is not required for exercise training‐induced angiogenesis in skeletal muscle.
Support or Funding Information
This study was supported by Grant‐in‐Aid for Challenging Exploratory Research (16K13019) and Grant‐in‐Aid for Scientific Research (B) (15H03080) (18H03153) to Mitsuharu Okutsu.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Muscle‐derived SDF‐1α/CXCL12 modulates endothelial cell proliferation but is not required for exercise training‐induced angiogenesis
- Creators
- Mitsuharu Okutsu - Nagoya City UniversityMami Yamada - Nagoya City UniversityChihiro Hokazono - Nagoya City UniversityKen Tokizawa - National Institute of Occupational Safety and HealthShuri Marui - Waseda UniversityMasahiro Iwata - Nihon Fukushi UniversityVitor A Lira - University of IowaKatsuhiko Suzuki - Waseda UniversityShinji Miura - University of ShizuokaKei Nagashima - Waseda University
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.33(S1), pp.lb433-lb433
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2019.33.1_supplement.lb433
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- Grant‐in‐Aid for Challenging Exploratory Research (16K13019) Grant‐in‐Aid for Scientific Research (15H03080; 18H03153)
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Health and Human Physiology
- Record Identifier
- 9984267150502771
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