title: Enalapril protects endothelial cells against induced apoptosis in Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a progressive neurodegenerative disease in which endothelial cell (EC) can be affected. In brain, functional changes in ECs contribute to reductions in resting blood flow. Furthermore, angiotensin-converting enzyme inhibitors (ACE-I) have beneficial effects on endothelial dysfunction. This is the first study that presents direct experimental evidence associating endothelial apoptosis as a basis of AD pathogenesis and response to an ACE-I therapy.
  
  
  METHODS
  Human umbilical vein ECs (HUVECs) were treated with sera from AD patients and sera from healthy volunteers (each group, n = 10). Apoptosis was determined by annexin V-propidium iodide staining and cell death detection kit. The effect of 50 μM enalapril on endothelial apoptosis was assessed. Nitrite (NO2 (-)) levels were determined in the culture supernatants.
  
  
  RESULTS
  Enalapril suppressed the induction of apoptosis by the serum of patients only when used before treating HUVECs with the sera of AD. Mean ± SD of apoptosis induction in the control group was 6.7 ± 3.69; in the group treated with sera of AD for 24 h was 47.78 ± 0.65; in the group wherein sera from AD was added (pretreatment) after exposure of HUVECs by 50 μM enalapril for 24 h was 26.6 ± 2.63; and in the group wherein HUVECs were exposed in the sera of AD for 24 h and then 50 μM enalapril was added to these cells for another 24 h (post-treatment) was 56.87 ± 5.51. Also, the mean ± SD of NO2 (-) concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media of untreated HUVECs by enalapril (1.03 ± 0.06) as compared with control (0.26 ± 0.13; P < 0.05), while the rate of nitric oxide (NO) significantly decreased when enalapril was presented in culture both in the pretreatment (0.07 ± 0.003) and in the post-treatment group (0.06 ± 0.005; P < 0.05).
  
  
  CONCLUSIONS
  It could be concluded that EC treated with sera from AD patients activates apoptosis in HUVECs; this effect was reversed by enalapril pretreatment. This can be proposed as a therapeutic approach for Alzheimer's patients.
authors: Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Medical Science, Islamic Azad University, Najafabad Branch, Isfahan, Iran.
authors: Rokhsareh
authors: R
authors: Meamar
authors: Leila
authors: L
authors: Dehghani
authors: Majid
authors: M
authors: Ghasemi
authors: Mohamad
authors: M
authors: Saadatnia
authors: Keivan
authors: K
authors: Basiri
authors: Nazanin Alaei
authors: NA
authors: Faradonbeh
authors: Shaghayegh Haghjooy
authors: SH
authors: Javanmard
keywords: Apoptosis; enalapril; endothelial cell
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