Author/Authors :
Meamar, Rokhsareh Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences , Ghasemi, Majid Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences , Saadatnia, Mohamad Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences , Basiri, Keivan Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences , Dehghani, Leila Department of Medical Science, Islamic Azad University, Najafabad Branch, 3Department neurology, Isfahan University of medical sciences , Alaei Faradonbeh, Nazanin Department of Medical Science, Young Researchers Club, Islamic Azad University, Najaf Abad Branch, 5Department of Physiology, Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan , Haghjooy Javanmard, Shaghayegh Department of Medical Science, Young Researchers Club, Islamic Azad University, Najaf Abad Branch, 5Department of Physiology, Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan
Abstract :
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. Materials and 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). Conclusion: 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.
