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Vascular
Complications of
Sickle Cell Anemia
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Some features of the vascular pathology of sickle cell disease
(retinopathy and nephropathy) resemble those observed in diabetic
patients. Diabetic microvascular complications are mediated by
advanced glycation end products (AGE) that, among other things,
enhance matrix protein cross-linking and result in basement membrane
thickening and luminal narrowing of blood vessels. It has been
shown that AGE synthesis is increased in the presence of reactive
oxygen species. Sickle cell disease is a condition of chronic oxidative stress
due to increased production of reactive oxygen species and decreased
activity of endogenous and exogenous antioxidant defense mechanisms.
We hypothesized that increased oxidative stress in sickle cell
patients could influence AGE formation and that AGE may play
a role in the etiology of the vascular pathology of sickle cell
disease. Circulating AGE Levels in Sickle Cell Disease Plasma and RBC AGE levels were measured by a non-competitive
chemiluminescent immunoassay using an AGE-specific antibody (Clone
6D12). Values for both plasma and RBC were significantly higher
in patients with sickle cell anemia (SCA) compared to controls
with normal hemoglobin phenotypes. These results show that circulating
AGE levels are elevated in sickle cell patients and suggest that
AGEs could play a role in the vasculopathy associated with the
disease. The goal of this project now is to determine the clinical
and biochemical relevance of AGEs in sickle cell pathophysiology.
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