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Ann Thorac Surg 2000;70:829-834
© 2000 The Society of Thoracic Surgeons

Original articles: cardiovascular

VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease

Christoph Kalka, MDa, Hassan Tehrani, MB, ChBa, Bernd Laudenberg, BSa, Peter R. Vale, MDa, Jeffrey M. Isner, MDa, Takayuki Asahara, MDa, James F. Symes, MDb

a Department of Vascular Medicine, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
b Department of Cardiothoracic Surgery, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA

Address reprint requests to Dr Symes, Division of Cardiothoracic Surgery, St. Elizabeth’s Medical Center, 11 Nevins St, MOB 306, Boston, MA 02135
e-mail: jsymes{at}semc.org

Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.

Background. Direct transfection of ischemic myocardium with naked plasmid DNA encoding for vascular endothelial growth factor-165 (VEGF165) has been shown to mobilize endothelial progenitor cells (EPCs). This study examined the kinetics of circulating EPCs isolated from peripheral blood mononuclear cells after gene transfer, and their role in neovascularization of ischemic myocardium.

Methods. The mononuclear cell population was isolated from peripheral venous blood samples of patients with functional class III or IV angina receiving intramyocardial VEGF165 gene transfer. Peripheral blood mononuclear cells were examined by an in vitro EPC culture assay and fluorescent-activated cell sorting. The data were compared with a control group consisting of patients who had undergone off-pump coronary artery bypass grafting without receiving gene transfer.

Results. Coinciding with a rise in VEGF levels, mobilization of EPCs increased significantly over base line for 9 weeks after the treatment (121 ± 14 cells/mm2 versus 36.8 ± 8 cells/mm2, p < 0.0005), followed by a subsequent decrease. Fluorescent-activated cell sorting analysis confirmed culture assay data, with a statistically significant rise in cells expressing vascular endothelial-cadherin, CD51/61 [{alpha}vß3], CD62E [E-selectin], CD34, and KDR. The control group failed to show significant mobilization of EPCs.

Conclusions. Mobilization of EPCs with resultant postnatal vasculogenesis, may play a role in revascularizing ischemic myocardium following human gene transfer with VEGF165.




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