Fiber type-specific differential expression of angiogenic factors in response to chronic hindlimb ischemia

D. Hunter Cherwek, M. Benjamin Hopkins, Michael J. Thompson, Brian H. Annex, Doris A. Taylor

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Alterations in endogenous levels of the angiogenic proteins basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were assessed in rabbit hindlimb muscles subjected to 1, 5, or 21 days of ischemia. In the glycolytic [tibialis anterior (TA)] and the oxidative [soleus (SOL)] muscles from the ischemic and contralateral (control) hindlimb, bFGF and VEGF protein expression was determined by ELISA and immunoblot analysis. Total VEGF protein expression was greater in oxidative than in glycolytic muscles after 5 days of hindlimb ischemia. In SOL muscle, total VEGF detected by ELISA in ischemic limbs was increased to 137, 300, and 220% of control at 1, 5, and 21 days, respectively. However, in TA, total VEGF expression by ELISA was increased only at 1 and 5 days of ischemia to 140 and 134% of control, respectively. By immunoblotting, the expression of the 165-amino acid isoform (VEGF165) was initially decreased to 55% of control in ischemic SOL at I day but was increased to 250% of control at day 5 and remained at 155% at day 21. In TA, VEGF165 was increased to 260% of control at i day of ischemia but only to 150% of control by day 5. The only significant change in bFGF expression in either the oxidative or glycolyric muscles was a small increase (129% of control) at 21 days in SOL. This study demonstrates that the magnitude and direction of change in VEGF protein expression depend on VEGF subtype, muscle fiber type, and duration of ischemia. These findings suggest that strategies in therapeutic angiogenesis may need to differ depending on muscle fiber type.

Original languageEnglish (US)
Pages (from-to)H932-H938
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number3 48-3
DOIs
StatePublished - 2000

Keywords

  • Angiogenesis
  • Basic fibroblast growth factor
  • Skeletal muscle
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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