Therapeutic myocardial angiogenesis with vascular endothelial growth factors

Youngsup Yoon, Ingrid A. Johnson, Jong Seon Park, Larry Diaz, Douglas W. Losordo

Research output: Contribution to journalReview article

52 Citations (Scopus)

Abstract

Emerging evidence has shown that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment tissue perfusion through neovascularization in animal models of myocardial and hindlimb ischemia. Many cytokines have angiogenic activity; one of those that have been best studied in animal models and clinical trials is vascular endothelial growth factor (VEGF). VEGF has been known to be a key regulator of physiologic and pathologic angiogenesis associated with tumor. Recently the effect of VEGF is not restricted to the direct angiogenic effect in vivo but includes mobilization of bone-marrow-derived endothelial progenitor cells and augmentation of postnatal vasculogenesis in situ. Clinical trials of therapeutic angiogenesis with VEGF in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials with recombinant protein (rhVEGF165) have been limited to intracoronary and intravenous administration and have shown favorable trends in exercise time and angina frequency. Small-scale, placebo-controlled, randomized clinical trials of gene transfer (phVEGF-2) via thoracotomy or percutaneous intramyocardial delivery demonstrated significant improvement of both subjective symptoms and objective measures of myocardial ischemia. Both therapeutic modalities appear to be safe and well tolerated. Further studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor cell or other stem cell supplementation, to provide safe and effective therapeutic myocardial neovascularization.

Original languageEnglish
Pages (from-to)63-74
Number of pages12
JournalMolecular and Cellular Biochemistry
Volume264
Issue number1-2
DOIs
Publication statusPublished - 2004 Sep 1

Fingerprint

Vascular Endothelial Growth Factors
Vascular Endothelial Growth Factor A
Gene transfer
Endothelial cells
Recombinant Proteins
Myocardial Ischemia
Intercellular Signaling Peptides and Proteins
Animals
Animal Models
Physiologic Neovascularization
Perfusion
Placebos
Clinical Trials
Pathologic Neovascularization
Exercise
Angiogenesis Inducing Agents
Thoracotomy
Therapeutics
Hindlimb
Stem cells

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Yoon, Youngsup ; Johnson, Ingrid A. ; Park, Jong Seon ; Diaz, Larry ; Losordo, Douglas W. / Therapeutic myocardial angiogenesis with vascular endothelial growth factors. In: Molecular and Cellular Biochemistry. 2004 ; Vol. 264, No. 1-2. pp. 63-74.
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Therapeutic myocardial angiogenesis with vascular endothelial growth factors. / Yoon, Youngsup; Johnson, Ingrid A.; Park, Jong Seon; Diaz, Larry; Losordo, Douglas W.

In: Molecular and Cellular Biochemistry, Vol. 264, No. 1-2, 01.09.2004, p. 63-74.

Research output: Contribution to journalReview article

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