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Acute and long term effect of Indoxyl sulfate on endothelial cells from healthy and damaged thoracic aorta (model of Chronic Kidney Disease)
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Introduction: Patients with chronic kidney disease (CKD) represent a group at high risk group for cardiovascular mortality and morbidity compared with the general population. Endothelial dysfunction, associated with loss of endothelial cells or overexpression of adhesion molecules, is one of the major contributors for this cardiovascular morbi-mortality. CKD is also characterized by an accumulation of uraemic toxins, such as indoxyl sulfate (IS). Most studies on this toxin have been performed on HUVECs cultures instead of ex vivo endothelial cells, which might give us more reliable results.
Methods: We prepared an ex vivo model, by which thoracic aorta from CKD and sham C57/BL6 mice were used to study the acute (30 min) effect of IS on endothelial dysfunction associated with chronic renal failure. The same model was used to study the long term (2 or 4 days) direct effects of IS in the onset of endothelial dysfunction.
Results and Discussion: CKD by itself was able to induce a small downgrade in PECAM-1 expression. IS was able to cause a concentration-dependent decrease on PECAM-1 expression in thoracic aorta from CKD mice. IS was also able to cause a concentration and time-dependent decrease on PECAM-1 expression in thoracic aorta from sham mice.
Conclusion: We demonstrated, with an ex-vivo model of CKD which used endothelial cells at the aortic root instead of HUVECs, that: 1) CKD by itself may be able to induce a small loss of endothelial cells; 2) IS may decrease the number of endothelial cells in CKD context, in a concentration-dependent effect; 3) IS may lead to a concentration and time-dependent decrease on the number of endothelial cells in sham CKD context, and would thus participate on the onset of CKD. It is imperative to continue studying the effect of IS in CKD and sham conditions with endothelial cell models, in order to better understand the mechanisms between CKD, IS, endothelial dysfunction and cell loss.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
Palavras-chave
Mestrado Integrado - 2014