NDLI: Stem cell factor gene transfer improves cardiac function after myocardial infarction in swine.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ishikawa, Kiyotake Fish, Kenneth Aguero, Jaume Yaniz-Galende, Elisa Jeong, Dongtak Kho, Changwon Tilemann, Lisa Fish, Lauren Liang, Lifan Eltoukhy, Ahmed A. Anderson, Daniel G. Zsebo, Krisztina Costa, Kevin D. Hajjar, Roger J.
Description	Author Affiliation: Ishikawa K ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Fish K ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Aguero J ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Yaniz-Galende E ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Jeong D ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Kho C ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Tilemann L ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Fish L ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Liang L ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Eltoukhy AA ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Anderson DG ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Zsebo K ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Costa KD ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.)); Hajjar RJ ( From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.))
Abstract	BACKGROUND: Stem cell factor (SCF), a ligand of the c-kit receptor, is a critical cytokine, which contributes to cell migration, proliferation, and survival. It has been shown that SCF expression increases after myocardial infarction (MI) and may be involved in cardiac repair. The aim of this study was to determine whether gene transfer of membrane-bound human SCF improves cardiac function in a large animal model of MI. METHODS AND RESULTS: A transmural MI was created by implanting an embolic coil in the left anterior descending artery in Yorkshire pigs. One week after the MI, the pigs received direct intramyocardial injections of either a recombinant adenovirus encoding for SCF (Ad.SCF, n=9) or ß-gal (Ad.ß-gal, n=6) into the infarct border area. At 3 months post-MI, ejection fraction increased by 12% relative to baseline after Ad.SCF therapy, whereas it decreased by 4.2% (P=0.004) in pigs treated with Ad.ß-gal. Preload-recruitable stroke work was significantly higher in pigs after SCF treatment (Ad.SCF, 55.5±11.6 mm Hg versus Ad.ß-gal, 31.6±12.6 mm Hg, P=0.005), indicating enhanced cardiac function. Histological analyses confirmed the recruitment of c-kit(+) cells as well as a reduced degree of apoptosis 1 week after Ad.SCF injection. In addition, increased capillary density compared with pigs treated with Ad.ß-gal was found at 3 months and suggests an angiogenic role of SCF. CONCLUSIONS: Local overexpression of SCF post-MI induces the recruitment of c-kit(+) cells at the infarct border area acutely. In the chronic stages, SCF gene transfer was associated with improved cardiac function in a preclinical model of ischemic cardiomyopathy.
File Format	HTM / HTML
ISSN	19413289
e-ISSN	19413297
DOI	10.1161/CIRCHEARTFAILURE.114.001711
Journal	Circulation: Heart Failure
Issue Number	1
Volume Number	8
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2015-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cardiology Genetic Therapy Myocardial Infarction Therapy Myocardium Metabolism Stem Cell Factor Stroke Volume Ventricular Function, Left Physiology Animals Disease Models, Animal Pathology Physiopathology Swine Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine

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