The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury

被引:27
作者
Anderson, Corey D. [1 ,2 ]
Heydarkhan-Hagvall, Sepideh [1 ]
Schenke-Layland, Katja [2 ]
Yang, Jin Quan [1 ]
Jordan, Maria C. [2 ]
Kim, Jeanne K. [2 ]
Brown, David A. [1 ]
Zuk, Patricia A. [1 ]
Laks, Hillel [1 ]
Roos, Kenneth P. [2 ]
MacLellan, W. Robb [2 ]
Beygui, Ramin E. [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Cardiovasc Res Labs, Los Angeles, CA 90095 USA
关键词
adult mesenchymal stem cells; hepatocyte growth factor (HGF); stromal cell-derived factor-1 alpha (CXCL12); myocardium; ischemia/reperfusion injury;
D O I
10.1016/j.jss.2007.08.005
中图分类号
R61 [外科手术学];
学科分类号
摘要
The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines, which modulate cardiomyocyte survival and function. MSCs express at least two cytoprotective cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha (CXCL12). The aim of our study was to compare the effects of these two cytokines administered acutely post-MI. We subjected adult male Lewis rats to myocardial ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left ventricular (LV) function revealed that LV ejection fraction was increased in the HGF treated group compared with the phosphate-buffered saline (PBS) control group. Likewise, LV end diastolic dimension was reduced in the HGF treated group compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk showed improved contractility and relaxation in the HGF treated group compared with the PBS control group. In contrast, no significant effect on LV function was seen in the CXCL12 treated group. To determine the potential mechanism for this effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in the HGF treated group compared with the PBS control group. Thus, HGF acutely post-MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI LV remodeling. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:164 / 171
页数:8
相关论文
共 35 条
[1]   Stromal cell-derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J].
Abbott, JD ;
Huang, Y ;
Liu, D ;
Hickey, R ;
Krause, DS ;
Giordano, FJ .
CIRCULATION, 2004, 110 (21) :3300-3305
[2]   Transcoronary transplantation of progenitor cells after myocardial infarction [J].
Assmus, Birgit ;
Honold, Joerg ;
Schaechinger, Volker ;
Britten, Martina B. ;
Fischer-Rasokat, Ulrich ;
Lehmann, Ralf ;
Teupe, Claudius ;
Pistorius, Katrin ;
Martin, Hans ;
Abolmaali, Nasreddin D. ;
Tonn, Torsten ;
Dimmeler, Stefanie ;
Zeiher, Andreas M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (12) :1222-1232
[3]   Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance [J].
Berry, Mark F. ;
Engler, Adam J. ;
Woo, Y. Joseph ;
Pirolli, Timothy J. ;
Bish, Lawrence T. ;
Jayasankar, Vasant ;
Morine, Kevin J. ;
Gardner, Timothy J. ;
Discher, Dennis E. ;
Sweeney, H. Lee .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (06) :H2196-H2203
[4]   Guidance of primordial germ cell migration by the chemokine SDF-1 [J].
Doitsidou, M ;
Reichman-Fried, M ;
Stebler, J ;
Köprunner, M ;
Dörries, J ;
Meyer, D ;
Esguerra, CV ;
Leung, T ;
Raz, E .
CELL, 2002, 111 (05) :647-659
[5]   Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells [J].
Gnecchi, M ;
He, HM ;
Liang, OD ;
Melo, LG ;
Morello, F ;
Mu, H ;
Noiseux, N ;
Zhang, LN ;
Pratt, RE ;
Ingwall, JS ;
Dzau, VJ .
NATURE MEDICINE, 2005, 11 (04) :367-368
[6]   Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement [J].
Gnecchi, Massimiliano ;
He, Huamei ;
Noiseux, Nicolas ;
Liang, Olin D. ;
Zhang, Lunan ;
Morello, Fulvio ;
Mu, Hui ;
Melo, Luis G. ;
Pratt, Richard E. ;
Ingwall, Joanne S. ;
Dzau, Victor J. .
FASEB JOURNAL, 2006, 20 (06) :661-669
[7]   DIRECT EVIDENCE THAT HEPATOCYTE GROWTH-FACTOR IS A HEPATOTROPHIC FACTOR FOR LIVER-REGENERATION AND HAS A POTENT ANTIHEPATITIS EFFECT INVIVO [J].
ISHIKI, Y ;
OHNISHI, H ;
MUTO, Y ;
MATSUMOTO, K ;
NAKAMURA, T .
HEPATOLOGY, 1992, 16 (05) :1227-1235
[8]   Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial [J].
Janssens, S ;
Dubois, C ;
Bogaert, J ;
Theunissen, K ;
Deroose, C ;
Desmet, W ;
Kolantzi, M ;
Herbots, L ;
Sinnaeve, P ;
Dens, J ;
Maertens, J ;
Rademakers, F ;
Dymarkowski, S ;
Gheysens, O ;
Van Cleemput, J ;
Bormans, G ;
Nuyts, J ;
Belmans, A ;
Mortelmans, L ;
Boogaerts, M ;
Van de Werf, F .
LANCET, 2006, 367 (9505) :113-121
[9]   HEPATOCYTE GROWTH-FACTOR PREVENTS ACUTE-RENAL-FAILURE AND ACCELERATES RENAL REGENERATION IN MICE [J].
KAWAIDA, K ;
MATSUMOTO, K ;
SHIMAZU, H ;
NAKAMURA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (10) :4357-4361
[10]  
Kehat I, 2001, J CLIN INVEST, V108, P407, DOI 10.1172/JCI200112131