Submitted on December 2, 2007
Accepted on October 31, 2008
Exercise-Induced Expression of VEGF and Salvation of Myocardium in the Early Stage of Myocardial Infarction
Guifu Wu1, Jamal S Rana2, Joanna Jadwiga Wykrzykowska3, Qingen Ke2, Peter M Kang4, Jian Li5, and Roger J Laham2*
1 Cardiology, The First Affiliated Hospital of Sun Yat-sen University, PR, China
2 Division of Cardiology, Beth Israel Deaconess Medical Center/ Harvard Medical School, Boston, Massachusetts, United States
3 Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
4 Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
5 Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: rlaham{at}bidmc.harvard.edu.
Background: The mechanism of exercise-induced benefit and angiogenesis in ischemic heart disease remains poorly defined. This study was designed to investigate the effects of exercise training on expression of angiogenic factors and angiogenesis, in infarcted myocardium (MI).
Methods and Results: Sixty-three male FVB mice were used for study and were divided into subgroups to test response to exercise: time-dependent expression of angiogenic factors to exercise training in normal (Group 1, n=12) and infarcted myocardium (Group 2, n=15) and exercise-induced angiogenic response in normal and infarcted myocardium (Group 3, n=20), as well as impact of exercise pre-conditioning on infarcted myocardium (Group 4, n=26). Exercise-training consisted of daily treadmill exercise for 1 hour for 3 days. VEGF and its receptors flt-1 and flk-1 expression was up-regulated by exercise training in mice with MI. Exercise-induced VEGF expression in MI group was higher than that in sham (control) group. Cell proliferation assessment showed significantly higher (p < 0.05) number of BrdU cells in post MI mice in exercise group as opposed to sedentary post MI mice. TTC staining disclosed a profound difference in the size of MI (18.25±2.93%) in exercise group vs. sedentary group (29.26±7.64%, p=0.02). Moreover exercise preconditioning before MI promoted VEGF expression, at both mRNA and protein levels.
Conclusion: Activation of VEGF and its receptors occurs in infarcted mice heart in response to exercise which results in decreased infarct size and improved angiogenesis.
