Linked Life Data

15522734

Source:http://linkedlifedata.com/resource/pubmed/id/15522734

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-11-3
pubmed:abstractText
Therapeutic vascular growth in the treatment of peripheral and myocardial ischemia has not yet fulfilled its expectations in clinical trials. Randomized, double-blinded placebo-controlled trials have predominantly shown the safety and feasibility but not the clear-cut clinically relevant efficacy of angiogenic gene or recombinant growth factor therapy. It is likely that growth factor levels achieved with single injections of recombinant protein or naked plasmid DNA are too low to induce any relevant angiogenic effects. Also, the route of administration of gene transfer vectors has not been optimal in many cases leading to low gene-transfer efficacy. Animal experiments using intramuscular or intramyocardial injections of adenovirus encoding vascular endothelial growth factor (VEGF, VEGF-A), the mature form of VEGF-D, and fibroblast growth factors (FGF-1, -2, and -4) have shown high angiogenic efficacy. Adenoviral overexpression of VEGF receptor-2 ligands, VEGF-A and the mature form of VEGF-D, enlarge the preexisting capillaries in skeletal muscle and myocardium via nitric oxide(NO)-mediated mechanisms and via proliferation of both endothelial cells and pericytes, resulting in markedly increased tissue perfusion. VEGF also enhances collateral growth, which is probably secondary to increased peripheral capillary blood flow and shear stress. As a side effect of VEGF overexpression and rapid microvessel enlargement, vascular permeability increases and may result in substantial tissue edema and pericardial effusion in the heart. Because of the transient adenoviral gene expression, the majority of angiogenic effects and side effects return to baseline by 2 weeks after the gene transfer. In contrast, VEGF overexpression lasting over 4 weeks has been shown to induce the growth of a persistent vascular network in preclinical models. To improve efficacy, the choice of the vascular growth factor, gene transfer vector, and route of administration should be optimized in future clinical trials. This review is focused on these issues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2660
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Gene transfer for therapeutic vascular growth in myocardial and peripheral ischemia.
pubmed:affiliation
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, Kuopio University, Kuopio, Finland.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't