HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Hattan, N. Articles by Weihrauch, D. Search for Related Content PubMed PubMed Citation Articles by Hattan, N. Articles by Weihrauch, D.

CALL FOR PAPERS
Cellular Plasticity in the Cardiovascular System

Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth

¹Department of Physiology, Cardiovascular Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112; and ²Department of Anesthesiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Submitted 12 February 2004 ; accepted in final form 31 March 2004

For therapeutic angiogenesis to achieve clinical relevance, it must be effective, with minimal side effects to other end organ systems. We developed a cardiac-specific gene delivery mechanism by transfecting autologous vascular smooth muscle cells (VSMC) with VEGF and administering these cells via intracoronary injection. We evaluated the efficacy of this protocol by its ability to stimulate angiogenesis in the presence of a subthreshold stimulus for collateralization. A modified canine repetitive coronary occlusion model was utilized in these experiments with left anterior descending coronary artery occlusions for 2 min every 2 h four times per day for 21 days. An intramyocardial catheter in the perfusion territory of the left anterior descending coronary artery measured proteins in the myocardial interstitial fluid. VSMC from jugular vein explants were isolated, amplified in culture for 3 wk, and transfected with a plasmid expressing VEGF-165 and/or enhanced green fluorescent protein. Cells were injected before commencement of occlusions. VEGF levels in myocardial interstitial fluid were significantly higher in VEGF-transfected animals than in sham (repetitive occlusions without cell transplantation) and control (repetitive occlusions with enhanced green fluorescent protein-transfected cells) animals at the onset of occlusions (P < 0.05). In the VEGF group, collateral flow was increased at day 7 and remained higher than in sham and control groups thereafter. We found that intracoronary administration of VEGF-transfected autologous VSMC effectively promotes collateral development. This approach may provide a way to confine delivery of a gene to a specified organ, thus minimizing complications related to gene transfection in nontargeted organ systems.

angiogenesis; coronary circulation; therapeutic angiogenesis

This article has been cited by other articles:

				H. K. Haider and M. Ashraf Bone marrow stem cell transplantation for cardiac repair Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2557 - H2567. [Abstract] [Full Text] [PDF]

				K. L. March and B. H. Johnstone Cellular approaches to tissue repair in cardiovascular disease: the more we know, the more there is to learn Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H458 - H463. [Full Text] [PDF]