Email updates

Keep up to date with the latest news and content from BMC Cardiovascular Disorders and BioMed Central.

Open Access Research article

Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation

Mei-pian Chen1, Shu-na Li1, Wendy WM Lam2, Yuen-chi Ho2, Shau-yin Ha1, Godfrey CF Chan1 and Yiu-fai Cheung13*

  • * Corresponding author: Yiu-fai Cheung xfcheung@hku.hk

  • † Equal contributors

Author Affiliations

1 Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

2 Department of Radiology, Queen Mary Hospital, Hong Kong, China

3 Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital 102, Pokfulam Road, Hong Kong, China

For all author emails, please log on.

BMC Cardiovascular Disorders 2014, 14:49  doi:10.1186/1471-2261-14-49

Published: 12 April 2014

Abstract

Background

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.

Methods and results

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.

Conclusions

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.

Keywords:
Thalassaemia; Ventricular rotation; Ventricular mechanics; Exercise echocardiography; Titin