Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction

Abstract

Laham RJ. Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction. Am J Physiol Heart Circ Physiol 296: H389 -H395, 2009. First published December 5, 2008; doi:10.1152/ajpheart.01393.2007.-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 the expression of angiogenic factors and angiogenesis in the infarcted myocardium [myocarial infaction (MI)]. Sixty-three male FVB mice were used for study and were divided into subgroups to test the response to exercise: the time-dependent expression of angiogenic factors to exercise training in normal (group 1; n ϭ 12) and infarcted myocardium (group 2; n ϭ 15) and the exerciseinduced angiogenic response in normal and infarcted myocardium (group 3; n ϭ 20) as well as the impact of exercise preconditioning on infarcted myocardium (group 4; n ϭ 26). Exercise training consisted of daily treadmill exercise for 1 h for 3 days. Expression of VEGF and its receptors Flt-1 and Flk-1 was upregulated by exercise training in mice with MI. Exercise-induced VEGF expression in the MI group was higher than that in the sham (control) group. Cell proliferation assessment showed a significantly higher (P Ͻ 0.05) number of bromodeoxyuridine-positive cells in post-MI mice in the exercise group as opposed to post-MI mice in the sedentary group. 2,3,5-Triphenyltetrazolium chloride staining revealed a profound difference in the size of MI (18.25 Ϯ 2.93%) in the exercise group versus the sedentary group (29.26 Ϯ 7.64%, P ϭ 0.02). Moreover, exercise preconditioning before MI promoted VEGF expression at both mRNA and protein levels. In conclusion, activation of VEGF and its receptors occurs in the infarcted mice heart in response to exercise, which results in decreased infarct size and improved angiogenesis.exercise; angiogenesis; ischemic heart disease; vascular endothelial growth factor EXERCISE AND PHYSICAL ACTIVITY are known to prevent the development of coronary artery disease and reduce symptoms in patients with established cardiovascular disease (26). In fact, a meta-analysis of 48 randomized trials of cardiac rehabilitation showed that, compared with the usual care, cardiac rehabilitation reduced total mortality by 20% and cardiac mortality by 26% (25). The precise mechanisms by which exercise therapy improves mortality in patients with coronary heart disease has not been fully elucidated (16,26). Exercise training has been shown to have beneficial effects on the coronary vasculature, including myocardial oxygen demand, endothelial function, autonomic tone, inflammatory markers, and the development of coronary collateral vessels (5, 28). However, the direct effect of exercise on myocardial angiogenesis in ischemic heart disease remains poorly defined.Angiogenesis is the process of formation of new blood vessels, which is mediated by angiogenic factors such as VEGF. Extensive studies have demonstrated that angiog...

Upregulation of Vascular Endothelial Growth Factor Expression in the Kidney Could Be Reversed Following Treadmill Exercise Training in Type I Diabetic Rats

“…Our findings are in agreement with the previous studies showing insignificant increase in VEGF expression in many tissues, such as skeletal muscles and heart, following endurance exercise training [26,34,35]. However, although VEGF protein expression significantly increased 1 day after exercise training in intact mice, it gradually returned to baseline after 4 days [36].…”

Intramuscular VEGF activates an SDF1-dependent progenitor cell cascade and an SDF1-independent muscle paracrine cascade for cardiac repair

“…This prosurvival paracrine mechanism may be particularly important in salvaging the failing heart, which exhibits ongoing cell death and tissue damage. Preconditioning by exercise, for instance, induces VEGF release from the working muscle, which results in decreased infarct size and improved angiogenesis (56). Our intramuscular VEGF therapeutic study lends support to this finding and provides mechanistic insight regarding the wholebody benefits of exercise.…”

“…In contrast, the skeletal muscle is endowed with an impressive ability to regenerate after injury, and this ability is coupled to paracrine production of many trophic factors possessing cardioprotective effects, which has increasingly been recognized (32,53,56). Taking advantage of this capacity of the skeletal muscle, we demonstrated an extracardiac therapeutic regimen based on intramuscular delivery of recombinant VEGF-A 165 for repair of the failing hamster heart (61).…”

Mouse model for myocardial injury caused by ischemia

“…A similar phenomenon was noted in the study of He Q et al on rat (He et al, 2003) and study of Guifu Wu et al on mice (Wu et al, 2009). …”