The Effect of Adiporon on Lipid Metabolism Genes Expression in Human Macrophages

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Resumo

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoproteins by the vascular wall macrophages. It leads to macrophage transformation into foam cells, accumulation of lipids in the intima of the arteries, atherosclerotic plaques development and following progression of cardiovascular diseases. Adiponectin, adipose tissue adipokine, has anti-atherogenic and anti-inflammatory effects that are mediated through binding to its receptors – AdipoR1 and AdipoR2. One of the mechanisms of adiponectin anti-atherogenic activity may be the participation in the regulation of reverse cholesterol transport and prevention of foam cells formation. We assumed that AdipoRon, a small-molecule adiponectin receptor agonist, could modulate the reverse cholesterol transport and inflammation genes expression in human macrophages. The aim of the present study was to investigate the effect of various concentrations of AdipoRon on the lipid metabolism ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRβ), PPARG, ACAT1 genes expression and inflammation IL6, TNFA, TLR4 genes expression in human macrophages. Primary human macrophages and THP-1 macrophages cell line were treated with various concentrations of AdipoRon. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, TLR4 mRNA levels in the primary human macrophages was assessed using real-time PCR. The increase of PPARG and ABCA1 mRNA levels was shown in the primary human macrophages after 5 and 10 μM A-dipoRon treatment for 24 h. At the same time high concentration (20 μM) of AdipoRon has cytotoxic effect on macrophages, especially, on THP-1 cell line. The effect of AdipoRon on human macrophages and the investigation of potential adiponectin receptor agonists is of interest, due to the search for new approaches to the prevention and treatment of atherosclerosis.

Sobre autores

I. Pobozheva

Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”; Pavlov First St.-Petersburg State Medical University

Autor responsável pela correspondência
Email: perhaps_to_be@mail.ru
Russia, 188300, Leningrad Region, Gatchina; Russia, 197022 , Saint-Petersburg

K. Dracheva

Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”; Pavlov First St.-Petersburg State Medical University

Email: perhaps_to_be@mail.ru
Russia, 188300, Leningrad Region, Gatchina; Russia, 197022 , Saint-Petersburg

S. Pchelina

Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”; Pavlov First St.-Petersburg State Medical University; Institute of Experimental Medicine

Email: perhaps_to_be@mail.ru
Russia, 188300, Leningrad Region, Gatchina; Russia, 197022 , Saint-Petersburg; Russia, 197376, Saint-Petersburg

V. Miroshnikova

Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”; Pavlov First St.-Petersburg State Medical University

Email: perhaps_to_be@mail.ru
Russia, 188300, Leningrad Region, Gatchina; Russia, 197022 , Saint-Petersburg

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Declaração de direitos autorais © И.А. Побожева, К.В. Драчева, С.Н. Пчелина, В.В. Мирошникова, 2023

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