Uryash Arkady, Mijares Alfredo, Esteve Eric, Adams Jose A, Lopez Jose R
Division of Neonatology, Mount Sinai Medical Center, Miami Beach, FL, United States.
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Front Physiol. 2021 May 4;12:658042. doi: 10.3389/fphys.2021.658042. eCollection 2021.
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and the development of a dilated cardiomyopathy (DCM), which is the leading cause of death in DMD patients. Despite knowing the cause of DMD, there are currently no therapies which can prevent or reverse its inevitable progression. We have used whole body periodic acceleration (WBPA) as a novel tool to enhance intracellular constitutive nitric oxide (NO) production. WBPA adds small pulses to the circulation to increase pulsatile shear stress, thereby upregulating endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) and subsequently elevating the production of NO. Myocardial cells from dystrophin-deficient 15-month old mice have contractile deficiency, which is associated with elevated concentrations of diastolic Ca ([Ca]), Na ([Na]), and reactive oxygen species (ROS), increased cell injury, and decreased cell viability. Treating 12-month old mice with WBPA for 3 months reduced cardiomyocyte [Ca] and [Na] overload, decreased ROS production, and upregulated expression of the protein utrophin resulting in increased cell viability, reduced cardiomyocyte damage, and improved contractile function compared to untreated mice.
杜兴氏肌肉营养不良症（DMD）的特征是进行性肌肉萎缩和扩张型心肌病（DCM）的发展，这是DMD患者死亡的主要原因。尽管已知DMD的病因，但目前尚无能够预防或逆转其不可避免进展的疗法。我们已将全身周期性加速（WBPA）作为一种新型工具来增强细胞内组成型一氧化氮（NO）的产生。WBPA向循环系统添加小脉冲以增加脉动剪切应力，从而上调内皮型一氧化氮合酶（eNOS）和神经元型一氧化氮合酶（nNOS），随后提高NO的产生。来自15个月大的肌营养不良蛋白缺陷小鼠的心肌细胞存在收缩功能缺陷，这与舒张期Ca（[Ca]）、Na（[Na]）和活性氧（ROS）浓度升高、细胞损伤增加以及细胞活力降低有关。与未治疗的小鼠相比，用WBPA治疗12个月大的小鼠3个月可减少心肌细胞[Ca]和[Na]过载，降低ROS产生，并上调抗肌萎缩蛋白的表达，从而提高细胞活力，减少心肌细胞损伤，并改善收缩功能。
