Faculty Collaboration Database

Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth. Am J Physiol Heart Circ Physiol 2004 Aug;287(2):H488-93

Date

07/28/2004

Pubmed ID

15277192

DOI

10.1152/ajpheart.00145.2004

Scopus ID

2-s2.0-3242656374 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

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.

Author List

Hattan N, Warltier D, Gu W, Kolz C, Chilian WM, Weihrauch D

Author

Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Cardiac Surgical Procedures
Coronary Circulation
Dogs
Female
Genetic Therapy
Green Fluorescent Proteins
Indicators and Reagents
Luminescent Proteins
Male
Muscle, Smooth, Vascular
Myocardium
Myocytes, Smooth Muscle
Neovascularization, Physiologic
Transfection
Vascular Endothelial Growth Factor A