Knockdown of mesenchymal stem cellderived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPAR/LXR/ABCA1…

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Int J Mol Med. 2021 Dec;48(6):208. doi: 10.3892/ijmm.2021.5041. Epub 2021 Oct 5.

ABSTRACT

Mesenchymal stem cell (MSC) therapy has potential applications in treating atherosclerosis and coronary heart disease (CAD). Previous studies have demonstrated that MSCs are the most preferable sources of therapeutic exosomes, which carry long noncoding RNAs and participate in the progression of atherosclerosis. The results of our previous bioinformatics study demonstrated that the levels of LOC100129516 were significantly upregulated in peripheral blood mononuclear cells obtained from patients with CAD. However, the biological role of LOC100129516 in the development of atherosclerosis remains to be elucidated. In the present study, THP1 cells were treated with oxidized lowdensity lipoproteins to induce foam cell formation in vitro. Reverse transcriptionquantitative PCR (RTqPCR) was performed to detect the levels of LOC100129516 in THP1 macrophagederived foam cells. In addition, an in vivo model of atherosclerosis was established using Apolipoprotein E (ApoE) knockout (ApoE/) mice. The results of the RTqPCR assays demonstrated that the levels of LOC100129516 were upregulated in THP1 macrophagederived foam cells. MSCderived exosomes were able to deliver small interfering (si)LOC100129516 to THP1 cells to reduce the levels of LOC100129516. Moreover, transfection of siLOC100129516 via exosomal delivery significantly decreased the levels of total cholesterol (TC), free cholesterol and cholesterol ester in THP1 macrophagederived foam cells. Exosomalmediated delivery of siLOC100129516 decreased TC levels and lowdensity lipoprotein levels in the ApoE/ atherosclerosis mouse model. Mechanistically, exosomalmediated delivery of siLOC100129516 promoted cholesterol efflux by activating the peroxisome proliferatoractivated receptor (PPAR)/liver X receptor (LXR)/phospholipidtransporting ATPase ABCA1 (ABCA1) signaling pathway in vitro and in vivo. Collectively, these results suggested that exosomalmediated delivery of siLOC100129516, in which the exosomes were derived from MSCs, promoted cholesterol efflux and suppressed intracellular lipid accumulation, ultimately alleviating the progression of atherosclerosis via stimulation of the PPAR/LXR/ABCA1 signaling pathway.

PMID:34608501 | DOI:10.3892/ijmm.2021.5041

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Knockdown of mesenchymal stem cellderived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPAR/LXR/ABCA1...