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.
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.
Keywords: Apoptosis; enalapril; endothelial cell.