Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
BMC Cardiovasc Disord. 2014 Apr 12;14:49. doi: 10.1186/1471-2261-14-49.
Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin.
In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products.
Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.
铁可能通过氧化应激损伤肌节蛋白。我们探讨了重型β地中海贫血患者的左心室（LV）扭转力学及其与心肌铁负荷的关系。我们使用 HL-1 细胞和 B6D2F1 小鼠模型进一步确定了铁负荷对巨大肌节蛋白titin 蛋白水解的影响。
在 44 名年龄为 25±7 岁的地中海贫血患者和 38 名健康对照者中，使用斑点追踪超声心动图在休息时测定 LV 扭转和扭转速度。在 32 名患者和 17 名对照者中进一步评估了亚最大运动试验期间 LV 扭转参数的变化。与对照组相比，患者的 LV 心尖旋转、扭转、收缩扭转速度和舒张解旋速度明显降低。心脏磁共振 T2*发现与休息时舒张解旋速度相关。与对照组相比，患者的静息和运动时的 LV 扭转和收缩、舒张解旋速度的增量明显较低。患者和对照组在静息和运动时 LV 收缩扭转和舒张解旋速度之间存在显著相关性。在铁过载的 HL-1 细胞和 B6D2F1 小鼠心室心肌中，肌节结构的 titin 染色模式变得紊乱。铁过载小鼠心肌组织的凝胶电泳进一步显示 titin 同工型的量明显减少，titin 降解产物增加。
重型β地中海贫血患者的静息和动态 LV 扭转力学受损。细胞和动物模型提示 titin 降解在铁过载诱导的 LV 扭转力学改变中起潜在作用。
