Endogenous expression of angiogenesis-related factors in response to muscle inju

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Mol Cell Biochem. 2007 Apr;298(1-2):151-9.

Endogenous expression of angiogenesis-related factors in response to

muscle injury.

Wagatsuma A.

Department of Biochemical Sciences, National Institute of Fitness

and Sports, 1, Shiromizu, Kanoya, Kagoshima, 891-2393, Japan

Gene therapy has developed a new strategy to treat a variety of

ischemic diseases using angiogenic growth factors. However, the

endogenous expression pattern of angiogenesis-related factors in

response to muscle injury is not fully characterized.

In the present study, we investigated the expression of angiogenesis-

related factors, vascular endothelial growth factor, angiopoietin-

1, -2, monocyte chemoattractant protein-1, and their receptors

during muscle regeneration. Mice underwent freeze injury, and then

the gastrocnemius muscles were isolated 1, 3, 5, 7, 10, 14, and 28

days after surgery. Generally, changes in gene expression were most

dramatic during the early stage of muscle regeneration, and were

attenuated as angiogenesis progressively developed and then returned

to steady-state levels.

VEGF mRNA began to increase from day 3 and peaked at day 5 after

muscle injury. VEGF receptors, Flt-1, KDR/Flk-1, and neuropilin-1

mRNAs were increased from 3- to 9-fold at day 3 after muscle injury.

At the same time, angiopoietin-1 and angiopoietin-2 mRNA were

increased by 3- and 15-fold respectively, concomitantly with an

increase in their receptors and Tie-2 mRNA. Finally, MCP-1 and CC-

chemokine receptor 2 mRNAs were sharply up-regulated by 1600- and

100-fold, respectively, at day 3 after muscle injury.

These results suggest that the molecular events implicated in

angiogenesis occur at an early stage of muscle regeneration.