Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells
Abstract
Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.
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Apelin yields several bioactive fragments, with APLN-13 exhibiting the highest potency.
“Following post-translational processing of its precursor, Apelin yields several bioactive fragments, with APLN-13 exhibiting the highest potency [62].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [62]
In vitro studies using human cells and tissues indicate that apelin-13 improves lipid metabolism, exerts anti-inflammatory effects by inhibiting IL-6, IL-1β, and TNF-α, and may help stabilize atherosclerotic plaques.
“In vitro studies using human cells and tissues indicate that apelin-13 improves lipid metabolism [62], exerts anti-inflammatory effects by inhibiting IL-6, IL-1β, and TNF-α, and may help stabilize atherosclerotic plaques [62,63].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [62]
Apelin-13 and its analogs are being explored for cardiovascular protection, given their ability to improve lipid metabolism, exert anti-inflammatory effects, and stabilize atherosclerotic plaques.
“Similarly, apelin-13 and its analogs are being explored for cardiovascular protection, given their ability to improve lipid metabolism, exert anti-inflammatory effects, and stabilize atherosclerotic plaques [62,63].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [62]
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“Following post-translational processing of its precursor, Apelin yields several bioactive fragments, with APLN-13 exhibiting the highest potency [62].”
- Authors
- Zhang, X., Ye, Q., Gong, D., Lv, Y., Cheng, H., Huang, C., Chen, L., Zhao, Z., Li, L., Wei, X., Zhang, M., Xia, X., Yu, X., Zheng, X., Wang, S., Wang, Z., & Tang, C.
- Affiliations
- University of South China (CN)
- ORCID
- Venue
- Acta Biochimica et Biophysica Sinica
- Published
- 2017-06-01
- Volume
- 49
- Issue
- 6
- Pages
- 530-540
- ISSN
- 1672-9145 (ISSN-L)
- OpenAlex
- W2606911851
- Cited by
- 47
- References
- 36
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 21 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 1
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biochimica et Biophysica Sinica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- apelin-13, lipoprotein lipase, atherosclerosis, foam cells, THP-1 cells, APJ receptor, protein kinase C alpha, miR-361-5p, microRNA regulation, lipid accumulation, inflammatory cytokines, cholesterol esters, atheroprotection
- MeSH terms
- Apelin Receptors, Foam Cells, Gene Expression Regulation, Humans, Lipoprotein Lipase, Macrophages, Signal Transduction, Cytokines, Inflammation Mediators, 3' Untranslated Regions, RNA Interference, MicroRNAs, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Protein Kinase C-alpha
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