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) All Versions of this Article: 290/4/H1393    most recent 00871.2005v1 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 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 Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Zhang, J. Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Zhang, J.

CALL FOR PAPERS
Regulation and Function of Stem Cells in the Cardiovascular System

Bioenergetic and functional consequences of stem cell-based VEGF delivery in pressure-overloaded swine hearts

¹Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota; and ²Department of Biochemistry, University at Buffalo, Buffalo, New York

Submitted 12 August 2005 ; accepted in final form 11 December 2005

In an established swine model of severe left ventricular (LV) hypertrophy (LVH), the bioenergetic and functional consequences of transplanting autologous mesenchymal stem cells (MSCs) overexpressing vascular endothelial growth factor (VEGF-MSCs) into the LV were evaluated; transplantation was accomplished by infusion of VEGF-MSCs into the interventricular cardiac vein. Specifically, the hypertrophic response to aortic banding was compared in seven pigs treated with 30 million VEGF-MSCs, eight pigs treated with 30 million MSCs without VEGF modification, and 19 untreated LVH pigs. Eight pigs without banding or cell transplantation (normal) were also studied. Four weeks postbanding, LV wall thickening (MRI), myocardial blood flow (MBF), high-energy phosphate levels (³¹P magnetic resonance spectroscopy), and hemodynamic measurements were obtained under basal conditions and during a catecholamine-induced high cardiac workstate (HCW). Although 9 of 19 untreated banded pigs developed clinical evidence of biventricular failure, no MSCs-treated animal developed heart failure. MSCs engraftment was present in both cell transplant groups, and both baseline and HCW MBF values were significantly increased in hearts receiving VEGF-MSCs compared with other groups (P < 0.05). During HCW, cardiac inotropic reserve (defined as the percent increase of rate pressure product at HCW relative to baseline) was normal in the VEGF-MSCs group and significantly decreased in all other banded groups. Additionally, during HCW, the myocardial energetic state [reflected by the phosphocreatine-to-ATP ratio (PCr/ATP)] of VEGF-MSCs-treated hearts remained stable, whereas in all other groups, PCr/ATP decreased significantly from baseline values (P < 0.05, each group). Myocardial von Willebrand factor and VEGF mRNA expressions and myocardial capillary density were significantly increased in VEGF-MSCs-treated hearts (P < 0.05). Hence, in the pressure-overloaded LV, transplantation of VEGF-MSCs prevents LV decompensation, induces neovascularization, attenuates hypertrophy, and improves MBF, myocardial bioenergetic characteristics, and contractile performance.

mesenchymal stem cells; left ventricular hypertrophy; metabolism; vascular endothelial growth factor; vessels; perfusion

This article has been cited by other articles:

				D. Zisa, A. Shabbir, M. Mastri, G. Suzuki, and T. Lee Intramuscular VEGF repairs the failing heart: role of host-derived growth factors and mobilization of progenitor cells Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1503 - R1515. [Abstract] [Full Text] [PDF]

				M. Saeed, A. Martin, A. Jacquier, M. Bucknor, D. Saloner, L. Do, P. Ursell, H. Su, Y. W. Kan, and C. B. Higgins Permanent Coronary Artery Occlusion: Cardiovascular MR Imaging Is Platform for Percutaneous Transendocardial Delivery and Assessment of Gene Therapy in Canine Model Radiology, November 1, 2008; 249(2): 560 - 571. [Abstract] [Full Text] [PDF]

				M. Saeed, A. Martin, P. Ursell, L. Do, M. Bucknor, C. B. Higgins, and D. Saloner MR Assessment of Myocardial Perfusion, Viability, and Function after Intramyocardial Transfer of VM202, a New Plasmid Human Hepatocyte Growth Factor in Ischemic Swine Myocardium Radiology, October 1, 2008; 249(1): 107 - 118. [Abstract] [Full Text] [PDF]

				J. Feygin, A. Mansoor, P. Eckman, C. Swingen, and J. Zhang Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1772 - H1780. [Abstract] [Full Text] [PDF]

				L. Zeng, Q. Hu, X. Wang, A. Mansoor, J. Lee, J. Feygin, G. Zhang, P. Suntharalingam, S. Boozer, A. Mhashilkar, et al. Bioenergetic and Functional Consequences of Bone Marrow-Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling Circulation, April 10, 2007; 115(14): 1866 - 1875. [Abstract] [Full Text] [PDF]