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Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis
- Source :
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 317:R770-R779
- Publication Year :
- 2019
- Publisher :
- American Physiological Society, 2019.
-
Abstract
- Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.
- Subjects :
- Male
0301 basic medicine
Chemokine
Physiology
Angiogenesis
Neovascularization, Physiologic
030204 cardiovascular system & hematology
Mice
03 medical and health sciences
0302 clinical medicine
Physical Conditioning, Animal
Physiology (medical)
Human Umbilical Vein Endothelial Cells
Animals
Humans
Medicine
Muscle, Skeletal
Pathological
Cell Proliferation
Mice, Knockout
biology
business.industry
Endothelial Cells
Skeletal muscle
Chemokine CXCL12
Cell biology
Mice, Inbred C57BL
Endothelial stem cell
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Capillary density
embryonic structures
biology.protein
business
Subjects
Details
- ISSN :
- 15221490 and 03636119
- Volume :
- 317
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Accession number :
- edsair.doi.dedup.....48338384b9e2fa0b229de05241fd0ccf