de Melo Brunno Lemes, Vieira Stella S, Antônio Ednei L, Dos Santos Luís F N, Portes Leslie A, Feliciano Regiane S, de Oliveira Helenita A, Silva José A, de Carvalho Paulo de Tarso C, Tucci Paulo J F, Serra Andrey J
Cardiac Physiology Laboratory, Federal University of São Paulo São Paulo, Brazil.
Biophotonic Laboratory, Nove de Julho University São Paulo, Brazil.
Front Physiol. 2016 Dec 5;7:541. doi: 10.3389/fphys.2016.00541. eCollection 2016.
Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks. Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling-ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance. Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility.
肺动脉狭窄(PAS)是一种先天性缺陷,可导致右心室(RV)流出道梗阻。目前,PAS治疗中存在一些负面问题:并非所有患者都适合手术;在成年过程中往往需要再次手术;轻度狭窄的患者后期可能会出现心脏不良反应。因此,寻找对抗PAS长期影响的方法成为当前的一个目标。在本研究中,我们评估了运动训练对接受PAS 9周的大鼠的心脏保护作用。运动使体能和右心室收缩功能得到改善。运动还减轻了PAS诱导的向心性腔室变化、舒张功能障碍和纤维化。在一个促生存信号中也报告了运动的额外益处,其中Akt活性增加,心肌细胞凋亡正常化。这些发现伴随着微小RNA-1下调和微小RNA-21上调。此外,运动与肌节蛋白α-MHC以及调节钙处理的蛋白——兰尼碱受体和肌浆网钙ATP酶2在心肌中的丰度增加有关,这支持了运动在改善心肌性能方面的潜在作用。我们的结果首次证明运动可以减轻实验性PAS中的右心室重塑。心脏保护作用与右心室功能、生存信号通路、细胞凋亡以及参与心肌收缩调节的蛋白的正向调节有关。