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Altered vascular function, arterial stiffness, and antioxidant gene responses in pediatric thalassemia patients.

Abstract
Patients with thalassemia major are susceptible to cardiovascular complications by mechanisms not fully understood. Although overt cardiovascular complications usually occur after puberty, their underlying pathogenesis may begin much earlier. This study investigated whether there were early changes in vascular endothelial function and arterial stiffness in young patients with beta-thalassemia and hemoglobin E, and whether these changes were associated with oxidative stress and expression of antioxidant genes. The study recruited 30 pediatric patients and 30 age-matched control subjects. Compared with the control subjects, the patients had increased levels of oxidant biomarkers including malondialdehyde, protein carbonyl, and non-transferrin-bound iron and a decreased glutathione redox ratio. There were clear signs of vascular endothelial dysfunction and increased arterial stiffness, as shown by marked suppression of forearm blood flow after reactive hyperemia and increased pulse-wave velocity in the trunk and legs. The changes in FBF were associated with oxidative stress markers and free iron. An adaptive antioxidant gene response was activated in blood mononuclear cells, as shown by upregulation of GCLC and Bach-1 mRNA but downregulation of heme oxygenase-1 and thioredoxin mRNA. The results highlight the vascular changes seen even in young patients during treatment. These changes were associated with oxidative stress and suggest an adaptive response that serves to protect host cells from further oxidative damage.
AuthorsPantipa Detchaporn, Upa Kukongviriyapan, Auemduan Prawan, Arunee Jetsrisuparb, Stephen E Greenwald, Veerapol Kukongviriyapan
JournalPediatric cardiology (Pediatr Cardiol) Vol. 33 Issue 7 Pg. 1054-60 (Oct 2012) ISSN: 1432-1971 [Electronic] United States
PMID22349676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Biomarkers
  • Malondialdehyde
  • Hemoglobin E
Topics
  • Adolescent
  • Antioxidants (metabolism)
  • Biomarkers (metabolism)
  • Blood Flow Velocity
  • Case-Control Studies
  • Child
  • Endothelium, Vascular (physiopathology)
  • Female
  • Forearm (blood supply)
  • Gene Expression
  • Hemoglobin E (metabolism)
  • Humans
  • Linear Models
  • Male
  • Malondialdehyde (blood)
  • Oxidative Stress (genetics)
  • Polymerase Chain Reaction
  • Protein Carbonylation
  • Statistics, Nonparametric
  • Ultrasonography, Doppler
  • Vascular Stiffness
  • beta-Thalassemia (genetics, physiopathology)

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