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Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty.
Hum Gene Ther. 2000 Jan 20; 11(2):263-70.HG

Abstract

Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl of DOTMA:DOPE liposomes. Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia.

Authors+Show Affiliations

A.I. Virtanen Institute, University of Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10680840

Citation

Laitinen, M, et al. "Catheter-mediated Vascular Endothelial Growth Factor Gene Transfer to Human Coronary Arteries After Angioplasty." Human Gene Therapy, vol. 11, no. 2, 2000, pp. 263-70.
Laitinen M, Hartikainen J, Hiltunen MO, et al. Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Hum Gene Ther. 2000;11(2):263-70.
Laitinen, M., Hartikainen, J., Hiltunen, M. O., Eränen, J., Kiviniemi, M., Närvänen, O., Mäkinen, K., Manninen, H., Syvänne, M., Martin, J. F., Laakso, M., & Ylä-Herttuala, S. (2000). Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Human Gene Therapy, 11(2), 263-70.
Laitinen M, et al. Catheter-mediated Vascular Endothelial Growth Factor Gene Transfer to Human Coronary Arteries After Angioplasty. Hum Gene Ther. 2000 Jan 20;11(2):263-70. PubMed PMID: 10680840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. AU - Laitinen,M, AU - Hartikainen,J, AU - Hiltunen,M O, AU - Eränen,J, AU - Kiviniemi,M, AU - Närvänen,O, AU - Mäkinen,K, AU - Manninen,H, AU - Syvänne,M, AU - Martin,J F, AU - Laakso,M, AU - Ylä-Herttuala,S, PY - 2000/2/19/pubmed PY - 2000/3/18/medline PY - 2000/2/19/entrez SP - 263 EP - 70 JF - Human gene therapy JO - Hum. Gene Ther. VL - 11 IS - 2 N2 - Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl of DOTMA:DOPE liposomes. Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia. SN - 1043-0342 UR - https://www.unboundmedicine.com/medline/citation/10680840/Catheter_mediated_vascular_endothelial_growth_factor_gene_transfer_to_human_coronary_arteries_after_angioplasty_ L2 - https://www.liebertpub.com/doi/full/10.1089/10430340050016003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -