Kolwicz Stephen C, MacDonnell Scott M, Renna Brian F, Reger Patricia O, Seqqat Rachid, Rafiq Khadija, Kendrick Zebulon V, Houser Steven R, Sabri Abdelkarim, Libonati Joseph R
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1361-8. doi: 10.1152/ajpheart.01253.2008. Epub 2009 Aug 7.
We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n = 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n = 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls (n = 18). Heart weight was greater in SHR-TRD vs. both WKY (P < 0.01) and SHR-SED (P < 0.05). Morphometric-derived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY (P < 0.001) and attenuated in SHR-TRD relative to SHR-SED (P < 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67(+) cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit(+) cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart.
我们研究了叠加于慢性高血压的运动训练如何影响左心室重塑。检测了雌性自发性高血压大鼠(SHR)心脏中的心肌细胞肥大、凋亡和增殖情况。将4个月大的SHR动物分为久坐组(SHR-SED;n = 18)或跑步机跑步组(SHR-TRD,速度20米/分钟,每天1小时,每周5天,共12周;n = 18)。年龄匹配的久坐Wistar Kyoto(WKY)大鼠作为对照(n = 18)。与WKY组(P < 0.01)和SHR-SED组(P < 0.05)相比,SHR-TRD组的心脏重量更大。与WKY组相比,SHR-SED组形态学测量得出的左心室前壁、后壁和室间隔厚度增加,而SHR-TRD组进一步增加。与WKY组相比,SHR-SED组心肌细胞表面积、长度和宽度增加,SHR-TRD组进一步增加。与WKY组相比,SHR-SED组钙调神经磷酸酶丰度增加(P < 0.001),与SHR-SED组相比,SHR-TRD组钙调神经磷酸酶丰度降低(P < 0.05)。各组间Akt的蛋白丰度和mRNA无差异。与WKY组相比,SHR-SED组的凋亡率增加,而SHR-TRD组凋亡率降低。各组间Ki-67(+)细胞丰度无统计学差异。与WKY组相比,SHR-TRD组心脏祖细胞(c-Kit(+)细胞)丰度增加。这些数据表明,尽管钙调神经磷酸酶丰度降低,但叠加于高血压的运动训练仍会加剧心肌细胞肥大。运动训练还减轻了高血压中的细胞凋亡,并显示出增加心脏祖细胞丰度的趋势,从而使运动训练的高血压心脏中的心肌细胞数量更有利。