Chirico Erica N, Ding Dennis, Muthukumaran Geetha, Houser Steven R, Starosta Tim, Mu Anbin, Margulies Kenneth B, Libonati Joseph R
School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania.
Temple University School of Medicine, Philadelphia, Pennsylvania.
Physiol Rep. 2015 Oct;3(10). doi: 10.14814/phy2.12566.
Stem cell therapy for myocardial infarction (MI) has been shown to improve cardiac function and reduce infarct size. Exercise training, in the form of cardiac rehabilitation, is an essential part of patient care post-MI. Hence, we tested the effects of acute and chronic aerobic exercise on stem cell retention and cardiac remodeling post-MI. Small epicardial MI's were induced in 12-month-old C57BL/6 mice via cryoinjury. Two weeks post-MI, vehicle infusion (N = 4) or GFP(+) bone marrow-derived cells (BMC) were injected (tail vein I.V.) immediately after acute exercise (N = 14) or sedentary conditions (N = 14). A subset of mice continued a 5-week intervention of chronic treadmill exercise (10-13 m/min; 45 min/day; 4 days/week; N = 7) or remained sedentary (N = 6). Exercise tolerance was assessed using a graded exercise test, and cardiac function was assessed with echocardiography. Acute exercise increased GFP(+) BMC retention in the infarcted zone of the heart by 30% versus sedentary (P < 0.05). This was not associated with alterations in myocardial function or gene expression of key cell adhesion molecules. Animals treated with chronic exercise increased exercise capacity (P < 0.05) and cardiac mass (P < 0.05) without change in left ventricular ejection fraction (LVEF), infarct size, or regional wall thickness (P = NS) compared with sedentary. While BMC's alone did not affect exercise capacity, they increased LVEF (P < 0.05) and Ki67(+) nuclei number in the border zone of the heart (P < 0.05), which was potentiated with chronic exercise training (P < 0.05). We conclude that acute exercise increases BMC retention in infarcted hearts and chronic training increases exogenous BMC-mediated effects on stimulating the cardiomyocyte cell cycle. These preclinical results suggest that exercise may help to optimize stem cell therapeutics following MI.
心肌梗死(MI)的干细胞治疗已被证明可改善心脏功能并减小梗死面积。以心脏康复形式进行的运动训练是心肌梗死后患者护理的重要组成部分。因此,我们测试了急性和慢性有氧运动对心肌梗死后干细胞滞留和心脏重塑的影响。通过冷冻损伤在12月龄C57BL/6小鼠中诱导小面积心外膜心肌梗死。心肌梗死后两周,在急性运动(N = 14)或久坐状态(N = 14)后立即经尾静脉注射载体(N = 4)或绿色荧光蛋白(GFP)阳性骨髓来源细胞(BMC)。一部分小鼠继续进行为期5周的慢性跑步机运动干预(10 - 13米/分钟;45分钟/天;4天/周;N = 7),或保持久坐(N = 6)。使用分级运动试验评估运动耐力,并用超声心动图评估心脏功能。与久坐相比,急性运动使梗死心脏区域的绿色荧光蛋白阳性骨髓来源细胞滞留增加30%(P < 0.05)。这与心肌功能或关键细胞粘附分子的基因表达改变无关。与久坐相比,接受慢性运动治疗的动物运动能力增加(P < 0.05)且心脏质量增加(P < 0.05),而左心室射血分数(LVEF)、梗死面积或室壁厚度无变化(P = 无显著差异)。虽然单独的骨髓来源细胞不影响运动能力,但它们增加了心脏边界区域的左心室射血分数(P < 0.05)和Ki67阳性细胞核数量(P < 0.05),慢性运动训练可增强这种作用(P < 0.05)。我们得出结论,急性运动增加梗死心脏中骨髓来源细胞的滞留,慢性训练增加外源性骨髓来源细胞对刺激心肌细胞细胞周期的作用。这些临床前结果表明,运动可能有助于优化心肌梗死后的干细胞治疗。