الفهرس 
Normal Endothelial structure and FunctionOnly 14 pages are availabe for public view
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Abstract
The thalassemias are heterogeneous group of genetic disorders of hemoglobin synthesis, all of which result from a reduced rate of production of one or more ofthe globin chains of hemoglobin. This basic defect results in imbalanced globin chain synthesis, which is the hallmark of all forms of thalassemia.
In β-thalassemia, the severity of the pathophysiology depends on the level of β-globin chain deficiency, which leads to an excess of α-globin chains.Consequently, thalassemic RBCs are hypochromic and microcytic and have a shorter half-life, leading to anemia.
Thalassemia major is characterized by chronic ineffective erythropoiesis and anemia as its primary problems. These, in turn, produce physiologic adaptations in the cardiovascular system as well as pathologic/iatrogenic processes such as iron overload, splenectomy, nutritional deficiencies, chronic oxidative stress, and lung disease.
Patients with thalassemia develop iron overload through increased iron absorption and transfusional therapy. Iron is toxic to all the endocrine glands that support the heart. Insulin resistance and frank diabetes are relatively common. Hyperglycemia and insulin resistance are powerful oxidative stressors to the heart, worsening the effects of iron overload. Proper insulin sensitivity is also vital for efficient cardiac energy utilization. Iron may also poison the thyroid and parathyroid gland, impairing metabolism and calcium regulation respectively. Iron-mediated adrenal insufficiency may also manifest itself during metabolic stress. Deficiencies of growth hormone and the sex steroids impair cardiac function. Iron-mediated endocrine toxicity must be excluded in TM patients with cardiac failure.
If thalassemia patients lived longer, the chronic effects of unbuffered oxidative stress on the vascular system are becoming more apparent.Thalassemia patients have impaired endothelial relaxation, intimal thickening, abnormal vascular stiffening, and degeneration of elastic arteries
This study demonstrates systemic arterial endothelial dysfunction and increased arterial stiffness in patients with β-thalassemia major. Importantly, these phenomena occur in the absence of cardiac dysfunction that is known to alter arterial endothelial function and vascular tone.
Endothelial dysfunction probably contributes in part to the increase in arterial stiffness, given the important role of endothelium-contraction.The present study provides evidence that arterial endothelial dysfunction occurs in vivo in patients with β-thalassemia major.
We have additionally demonstrated that arterial stiffness is
increased in both central elastic arteries and peripheral conduit arteries in patients with β-thalassemia major.
Stiffness of brachial artery is inversely related to the magnitude of flow-mediation dilation in our patients. Serum ferritin level does not correlate with the degree of arterial stiffness or impairment of flow-mediated dilation.
Because the brachial artery flow is not similar between patients and controls, the wall shear stress induced during reactive hyperemia to cause flow-mediated vasodilation is likely to be significantly different between the 2 groups.