effect of pioglitazone on the Alzheimer's disease-induced apoptosis in human umbilical vein endothelial cells

ABSTRACT

Alzheimer's disease [AD] is a progressive neurodegenerative disease and nowadays the role of endothelial cell [EC] injury has been proposed in pathological process in AD. Peroxisome proliferator-activated receptor- gamma [PPAR- gamma] agonist has anti-inflammatory properties through activation in glial cells and improves vascular function and prevent atherosclerotic disease progression. The aim of this study is evaluation of pioglitazone effects as a drug of PPAR- gamma agonist on endothelial apoptosis induced by sera from AD patients. Human umbilical vein endothelial cells [HUVECs] were treated with sera from AD patients [n = 10] and sera from controls [n = 10]. Apoptosis was identified by annexin V-propidium iodide staining and cell death detection kit. Apoptosis was evaluated after and before adding of 10 micro M pioglitazone on EC. Nitrite [NO[2]] levels were determined in the culture supernatants. Induced apoptosis by the serum of patients was inhibited markedly when pioglitazone used before treating HUVECs with the sera of AD. Also, the measurement of nitrite concentration showed significantly greater levels of dissolved NO[2]/NO[3] metabolite in the culture media of HUVECs treated by sera of AD patients [P < 0.05], while the rate of nitric oxide significantly decreased when pioglitazone exists in culture media. Further studies are justified to investigate the novel role of the PPARs in the prevention of the neuronal and endothelial damage in neurological disorder and present a new therapeutic approach for Alzheimer's patients