Lectin-like Oxidized LDL Receptor-1 (LOX-1) Protein Vaccination Reduces Inflammation and Attenuates Atherosclerosis Progression in Atherogenic-Diet Wistar Rats
Journal Title: International Cardiovascular Research Journal - Year 2016, Vol 10, Issue 4
Abstract
Background: Atherosclerosis is the main cause of cardiovascular disease, which has no effective preventive treatments. Lectin-like Oxidized LDL Receptor-1 (LOX-1) is a major receptor of ox-LDL in endothelial cells and plays an important role in atherosclerosis. Objectives: This research aimed to determine the role of LOX-1 protein vaccination in inhibiting atherosclerosis plaque progression through measurement of foam cells number and aorta wall thickness and reducing inflammation through Nuclear Factor– kappa B (NF-κB) activation and endothelial Nitric Oxide Synthase (eNOS) expression. Materials and Methods: This experimental study was conducted on seven groups of 28 male Wistar rats aged 6 to 8 weeks, including negative control group (normal diet rats), positive control group (atherogenic diet rats without vaccination), and 4 other experimental groups receiving atherogenic diet and LOX-1 vaccine containing 1, 10, 100, and 1000 ng LOX-1. Vaccination was performed on days 0, 21, and 35. The vaccines were also supplemented by aluminum hydroxide (alum) as an adjuvant. Finally, the 7th group only received atherogenic diet and alum. On the 57th day, the rats were euthanatized and their serum anti-LOX-1 IgG level, NF-κB activation, eNOS expressions, foam cells number, and aorta wall’s thickness were measured. After all, the data were analyzed using the SPSS statistical software, version 20 and P < 0.05 was considered to be statistically significant. Results: The results indicated that the vaccine was unable to raise the anti-LOX-1 IgG level significantly (P = 0.010). However, it was able to inhibit foam cells formation and aorta wall’s thickness significantly (P = 0.001). Furthermore, LOX-1 vaccination could significantly inhibit the activation of NF-κB (P = 0.001) and increase eNOS expression (P = 0.001). Conclusions: LOX-1 vaccine could potentially inhibit atherosclerosis by decreasing NF-κB activation, increasing eNOS expression, and inhibiting atherosclerosis plaques progression. Although the vaccine did not induce humoral immune response, it successfully inhibited the progression of atherosclerosis. Thus, it was predicted to work through other mechanisms, such as inducing cellular immune response.
Authors and Affiliations
Oktavia Rahayu Adianingsih, Fredo Tamara, Ardina Pramesti Putri, Angi Nurkhairina, Thoha Muhajir Albaar, Maimun Zulhaidah Arthamin, Valentina Yurina
Keywords
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