Nogueira-Ferreira Rita, Moreira-Gonçalves Daniel, Silva Ana Filipa, Duarte José Alberto, Leite-Moreira Adelino, Ferreira Rita, Henriques-Coelho Tiago
QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
Int J Cardiol. 2016 Jan 15;203:858-66. doi: 10.1016/j.ijcard.2015.11.066. Epub 2015 Nov 10.
Exercise training has been recognized as a non-pharmacological therapeutic approach in several chronic diseases; however it remains to be tested if exercise preconditioning can positively interfere with the natural history of pulmonary arterial hypertension (PAH). This is important since the majority of these patients are diagnosed at advanced stages of the disease, when right ventricle (RV) impairment is already present.
In the current study, we evaluated the preventive effect of exercise preconditioning on RV failure secondary to PAH, with a focus on the signaling pathways modulated by pro-inflammatory cytokines from TNF superfamily.
We analyzed the RV muscle from adult male Wistar rats exposed to a 4-week treadmill exercise training or sedentary regime, prior to the administration of monocrotaline (MCT) to induce PAH or with saline solution (controls).
Data indicate that exercise preconditioning prevented cardiac hypertrophy and RV diastolic dysfunction. At a molecular level, exercise modulated the TWEAK/NF-κB signaling axis and prevented the shift in MHC isoforms towards an increased expression of beta-MHC. Exercise preconditioning also prevented the increase of atrogin-1 expression, and induced a shift of MMP activity from MMP-9 to MMP-2 activity.
Altogether, data support exercise as a preventive strategy for the management of PAH, which is of particular relevance for the familial form of PAH that is manifested by greater severity or earlier onset.
运动训练已被公认为是几种慢性疾病的非药物治疗方法；然而，运动预处理是否能积极干预肺动脉高压（PAH）的自然病程仍有待验证。这一点很重要，因为这些患者中的大多数在疾病晚期才被诊断出来，此时右心室（RV）已经出现损伤。
在本研究中，我们评估了运动预处理对PAH继发的RV衰竭的预防作用，重点关注由TNF超家族的促炎细胞因子调节的信号通路。
我们分析了成年雄性Wistar大鼠的RV肌肉，这些大鼠在给予单氰胺（MCT）诱导PAH或生理盐水（对照组）之前，接受了为期4周的跑步机运动训练或久坐不动。
数据表明，运动预处理可预防心脏肥大和RV舒张功能障碍。在分子水平上，运动调节了TWEAK/NF-κB信号轴，并防止了MHC亚型向β-MHC表达增加的转变。运动预处理还可防止atrogin-1表达增加，并诱导MMP活性从MMP-9向MMP-2活性转变。
总之，数据支持运动作为PAH管理的预防策略，这对于以更严重或更早发作为特征的家族性PAH尤为重要。
