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Vascular Growth in Ischemic Limbs: A Review of Mechanisms and Possible Therapeutic Stimulation

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Author: Weel, V. van · Tongeren, R.B. van · Hinsbergh, V.W.M. van · Bockel, J.H. van · Quax, P.H.A.
Institution: TNO Kwaliteit van Leven
Source:Annals of Vascular Surgery, 4, 22, 582-597
Identifier: 240898
doi: doi:10.1016/j.avsg.2008.02.017
Keywords: Health · Biomedical Research · adenovirus vector · angiogenic factor · fibrin · fibroblast growth factor · fibroblast growth factor 4 · granulocyte macrophage colony stimulating factor · placebo · plasmid vector · protein · scatter factor · vasculotropin · vasculotropin 121 · vasculotropin 165 · vasculotropin A · vasculotropin C · angiogenesis · autologous bone marrow transplantation · bone marrow · Buerger disease · cell therapy · clinical trial · comprehension · coronary artery disease · diabetes mellitus · gene therapy · human · immune system · inflammatory cell · intermittent claudication · introspection · limb ischemia · neovascularization (pathology) · nonhuman · pain · peripheral occlusive artery disease · priority journal · review · stem cell · stenosis · stimulation · Angiogenesis Inducing Agents · Animals · Collateral Circulation · Gene Therapy · Humans · Ischemia · Leg · Neovascularization, Physiologic · Stem Cell Transplantation · Vascular Endothelial Growth Factor A


Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into mechanisms of vascular growth in the adult, in particular the role of angiogenic factors, the immune system, and bone marrow, were reviewed, together with modes of its therapeutic stimulation and results from recent clinical trials. Three concepts of vascular growth have been described to date-angiogenesis, vasculogenesis, and arteriogenesis (collateral artery growth)-which represent different aspects of an integrated process. Stimulation of arteriogenesis seems clinically most relevant and has most recently been attempted using autologous bone marrow transplantation with some beneficial results, although the mechanism of action is not completely understood. Better understanding of the highly complex molecular and cellular mechanisms of vascular growth may yet lead to meaningful clinical applications. © 2008 Annals of Vascular Surgery Inc.