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Administration of Vascular Endothelial Growth Factor Adjunctive to Fetal Cardiomyocyte Transplantation and Improvement of Cardiac Function in the Rat Model

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Sebastian Breuer, PhD

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Raja Al Dashti, MD

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Nasir Sulemanjee, MD

Division of Cardiology, The University of Texas Medical Branch, Galveston, Texas

Peter Hanrath, MD

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Christian Weber, MD

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Barry F. Uretsky, MD

Division of Cardiology, The University of Texas Medical Branch, Galveston, Texas

Ernst R. Schwarz, MD, PhD

Medical Clinic and Department of Molecular Cardiovascular Research, Department of Cardiology, RWTH University Hospital, Aachen, Germany and Division of Cardiology, The University of Texas Medical Branch, Galveston, Texas

Background: The functional impact of cellular transplantation and the potential role of the addition of angiogenic factors for survival of engrafts remain controversial.

Methods: Vascular endothelial growth factor (VEGF) (25 ng/mL) was added to cultured fetal cardiomyocytes labeled with bromodeoxyuridine (BrDU), which was injected into the border zones of myocardial infarction 4 weeks after coronary occlusion in rat hearts. Group 1 (n = 12) received cells plus VEGF protein (100 ng), group 2 (n = 12) received cells without VEGF, group 3 (n = 10) received VEGF without cells, and group 4 (n = 12) received pure culture medium. Cardiac function was then assessed by transthoracic two-dimensional echocardiography and Langendorff perfusion system. In situ hybridization for Y chromosomes of transplanted cells, detection of BrDU-labeled cells, and platelet/endothelial cell adhesion molecule-1 (PECAM-1) staining for endothelial cells was performed.

Results: Echocardiography revealed smaller end-diastolic left ventricular dimensions in transplanted hearts in group 1 (0.83 ± 0.13 cm 4 weeks after coronary occlusion before transplantation and 0.69 ± 0.14 cm 2 months after transplantation, P < .05) and in group 2 (0.88 ± 0.09 cm after coronary occlusion before transplantation and 0.76 ± 0.08 cm 2 months after transplant), and increases in fractional shortening (34.2% ± 8.53% before transplant and 45.3% ± 10.9% after [P < .05] in group 1; 26.9% ± 6.02% before transplant and 37.15% ± 8.08% after [P < .005] in group 2), whereas groups 3 and 4 showed a decrease in fractional shortening. Transplanted hearts developed higher pressures at rest (group 1, 96.8 ± 20.8 mm Hg; group 2, 98.6 ± 21.9 mm Hg) compared with controls (group 4, 70.9 ± 25 mm Hg) (P < .05) and during inotropic stimulation (group 1, 111 ± 19.5 mm Hg and group 2, 113.3 ± 32.6 vs group 4, 80.7 ± 31.6 mm Hg, P < .05). Histologic analysis demonstrated the presence of transplanted cells in border zones of infarcted host myocardium with neovascularization in all transplanted hearts.

Conclusion: Transplantation of fetal cardiomyocytes results in improvement of left ventricular function. The addition of VEGF does not contribute to further improvement of left ventricular function and angiogenesis in the present model.

Key Words: cardiomyocytes • cell transplantation • VEGF • myocardial infarction • angiogenesis • cardiac function

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 10, No. 1, 55-66 (2005)
DOI: 10.1177/107424840501000107


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