Circulating Endothelial and Endothelial Progenitor Cells, Arterial Function, and Ventriculo-Arterial Interaction in Patients with Beta-Thalassaemia Major

Professor Cheung, Yiu Fai   (Principal Investigator (PI))

Dr Ha Shau Yin   (Co-Investigator)

Professor Chan Godfrey Chi Fung   (Co-Investigator)

Dr Yang Mo   (Co-Investigator)

24

2008-09-01

58862

Circulating Endothelial and Endothelial Progenitor Cells, Arterial Function, and Ventriculo-Arterial Interaction in Patients with Beta-Thalassaemia Major

arterial function, endothelial cell, thalassaemia

Cardiovascular Research,Blood/Hematology

200807176058

Small Project Funding

2008

Completed

While ventricular dysfunction secondary to iron overload in patients with beta-thalassaemia major is well documented, accumulating evidence suggests coexistence of systemic arterial dysfunction. In these patients, we and others have demonstrated endothelial dysfunction and arterial stiffening as evidenced by reduced brachial arterial flow-mediated dilation, increased stiffness of the carotid artery, ascending aorta, and abdominal aorta, and reduced strain and distensibility of the ascending aorta. Importantly, endothelial dysfunction contributes to arterial stiffening through alteration of the vasomotor tone by reducing availability of endothelium-derived vasodilating substances. With regard to the integrity and functioning of the vascular endothelium, a current theory is that increased number of circulating endothelial cells (CECs) reflects severe endothelial damage and that therefore areas of the denuded subendothelium predisposes to disease processes as atherosclerosis. In parallel is the hypothesis that endothelial progenitor cells (EPCs) are restorative cells that possibly destined to replace or renew damaged areas of the intima. In patients with beta-thalassaemia major, the relationships between circulating endothelial and endothelial progenitor cells, arterial function, and ventriculo-arterial interaction, are hitherto unknown. In vitro studies have provided direct evidence that angiotensin II accelerates onset of EPC senescence via reactive oxygen species production. In a rodent model of iron overload, increased generation of reactive oxygen species within the arterial wall has been similarly demonstrated. Taken together, iron overload in patients with beta-thalassaemia major may potentially lead to disequilibrium between vascular injury and repair. The proposed study is, to the best of our knowledge, the first to quantify both CECs and EPCs simultaneously in patients with beta-thalassaemia major and to determine their relationships with functional indices of arterial and cardiac function. Furthermore, to address the issue of iron overload on levels of CECs and EPCs, these parameters would be compared to those of healthy controls and beta thalassaemia major patients who had undergone bone marrow transplantation and iron depletion therapy. This would also be the first study to use the novel techniques for assessment of endothelial injury, repair, and function in thalassaemia patients after successful bone marrow transplantation. The objectives of the present study are to determine in patients with beta-thalassaemia major: A) the effect of iron overload on quantities of CECs and EPCs and function of EPCs, B) the relationships between levels of CECs and EPCs and indices of arterial function in vivo C) the relationships between indices of left ventricular function and arterial parameters, and D) the impact of bone marrow transplantation followed by phlebotomy on quantities of CECs and EPCs, function of EPCs, and arterial function in vivo