J Biomed Res.  2014 Dec;15(4):156-161. 10.12729/jbr.2014.15.4.156.

Angiogenic effects of recombinant thymosin beta4 in a mouse hindlimb ischemia model

Affiliations
  • 1College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763, Korea. jkkang@chungbuk.ac.kr

Abstract

Recombinant thymosin beta4 (rTbeta4) has been reported to migrate and promote vascularization, wound-healing, and hair growth in a mouse hindlimb ischemia model of peripheral vascular disease. C57BL/6 mice (11-weeks-old) were anesthetized and an ischemic model was made by cutting the right aorta femoralis. The ischemic group was intraperitoneally administered with saline (300 microL/mouse) and the muscular administration group received rTbeta4 (150 microg in 300 microL of saline) or rTbeta4 (150 microg in 300 microL saline) to the abdominal cavity at 3-day intervals for 21 days. Myoatrophy of the ischemic group was observed compared to the normal control group. Generation of adjacent vessels was carried out in the rTbeta4 administration group compared to the ischemic group. The biopsy results showed significant fibrosis around the muscular undersurface and perimysium in the musculus quadriceps femoris of the ischemic group, whereas partial fibrosis was observed in the perimysium and endomysium in the rTbeta4 administration group. Immunostaining indicated that expression levels of hypoxiainducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor-1 (VEGF-1), and endothelial nitric oxide synthase (eNOS) in the rTbeta4 group were higher than those of the ischemic group. Western blotting showed that expression levels of HIF-1alpha, VEGF-1, and eNOS in the rTbeta4 group were higher than those of the ischemic group. In conclusion, rTbeta4 increases expression levels of HIF-1alpha, VEGF-1, and eNOS, resulting in angiogenesis.

Keyword

gene recombination thymosin beta4; Peripheral arterial disease (PAD); angiogenesis; Hindlimbschemia; vascular endothelial growth factor (VEGF)

MeSH Terms

Abdominal Cavity
Animals
Aorta
Biopsy
Blotting, Western
Fibrosis
Hair
Hindlimb*
Ischemia*
Mice*
Nitric Oxide Synthase Type III
Peripheral Vascular Diseases
Quadriceps Muscle
Thymosin*
Nitric Oxide Synthase Type III
Thymosin
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