The Role of Cytoprotective Cytokines in Cardiac Ischemia/Reperfusion Injury

Anderson, Corey D.; Heydarkhan-Hagvall, Sepideh; Schenke-Layland, Katja; Yang, Jin Quan; Jordan, Maria C.; Kim, Jeanne K.; Brown, David A.; Zuk, Patricia A.; Laks, Hillel; Roos, Kenneth P.; MacLellan, W. Robb; Beygui, Ramin E.

doi:10.1016/j.jss.2007.08.005

« Previous Next »Journal of Surgical Research
Volume 148, Issue 2 , Pages 164-171, August 2008

The Role of Cytoprotective Cytokines in Cardiac Ischemia/Reperfusion Injury

Corey D. Anderson, M.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
Sepideh Heydarkhan-Hagvall, Ph.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
Katja Schenke-Layland, Ph.D.
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
Jin Quan Yang, M.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
Maria C. Jordan, M.D.
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
Jeanne K. Kim, B.Sc.
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
David A. Brown, B.Sc.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
Patricia A. Zuk, Ph.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
Hillel Laks, M.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
Kenneth P. Roos, Ph.D.
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
W. Robb MacLellan, M.D.
- The Cardiovascular Research Laboratories, Department of Medicine and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
Ramin E. Beygui, M.D.
- Department of Surgery, Cardiothoracic Surgery Division, David Geffen School of Medicine, University of California, Los Angeles, California
- To whom correspondence and reprint requests should be addressed at Department of Surgery, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-1741.

Received 9 May 2007 published online 03 September 2007.

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 α (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.

Key Words: adult mesenchymal stem cells, hepatocyte growth factor (HGF), stromal cell-derived factor-1 α (CXCL12), myocardium, ischemia/reperfusion injury