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Updated: Feb 28, 2026

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Role of simvastatin and RORα activity in the macrophage apoptotic pathway
Neslihan Çoban1, Çağrı Güleç, Bilge Özsait Selçuk
1Department of Genetics, Institute for Experimental Medicine, İstanbul University; İstanbul-Turkey. neslic@istanbul.edu.tr.
Insights
Simvastatin may induce macrophage apoptosis, a key factor in atherosclerosis. Retinoic acid receptor-related orphan receptor alpha (RORα) ligands might partially counteract this effect, suggesting a potential therapeutic avenue.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Pharmacology
Background:
- Atherosclerosis is a leading global cause of mortality, characterized by chronic inflammation and plaque development.
- Macrophages are central players in atherosclerotic plaque formation and progression.
- The role of apoptosis in atherosclerosis remains complex and debated.
Purpose of the Study:
- To investigate the impact of simvastatin and retinoic acid receptor-related orphan receptor alpha (RORα) ligands on macrophage apoptosis.
- To explore the potential modulatory role of RORα in simvastatin-induced apoptosis.
Main Methods:
- Chromatin immunoprecipitation (ChIP) to assess RORα binding to apoptotic gene promoters in THP-1 cells.
- Treatment of THP-1 macrophage cells with simvastatin and RORα ligands (CPG52608, SR1001).
- Analysis of cell viability and count following treatments.
Main Results:
- Simvastatin and RORα ligands tended to reduce THP-1 macrophage viability.
- Simvastatin significantly decreased cell viability and count (p<0.05).
- RORα ligands partially attenuated the negative effects of simvastatin on cell viability.
Conclusions:
- Simvastatin may induce apoptosis in macrophages, a process potentially influenced by RORα.
- The RORα ligand SR1001 may modulate simvastatin-induced macrophage apoptosis.
- Further research is needed to elucidate RORα's precise role in regulating apoptotic pathways in this context.
Objective:
Atherosclerosis is a chronic inflammatory condition and is one of the main causes of death worldwide. Macrophages play important roles in the formation of atherosclerotic plaques. Apoptosis is progressively observed while plaques develop, although the precise mechanisms and outcomes of apoptosis in atherosclerosis development and progression are still contradictory. This study was conducted to explore the effects of simvastatin and retinoic acid receptor-related orphan receptor alpha (RORα) ligands on apoptosis in human acute monocytic leukemia (THP-1) macrophage cells.
Methods:
Briefly, the occupancy of RORα in the promoter regions of apoptotic pathway genes was demonstrated in THP-1 cell lines using chromatin immunoprecipitation (ChIP) analysis. In order to modulate RORα activity, THP-1 macrophage cells were treated with specific ligands (CPG52608 and SR1001) and then viability as well as count of THP-1 macrophage cells were analyzed.
Results:
We observed that simvastatin and both RORα ligands had a tendency to decrease THP-1 macrophage cell viability in culture. When compared with non-treated controls, simvastatin significantly decreased cell viability (p=0.04) and cell count (p=0.03). However, this negative effect of simvastatin seemed to be partly prevented by RORα ligands. In addition, bioinformatics analysis of ChIP-on-chip data demonstrated that several genes that are involved in the apoptotic pathway were likely RORα target genes. These genes were involved in the regulation of apoptosis through various pathways.
Conclusion:
In summary, our study suggest that simvastatin-mediated macrophage apoptosis might be modulated by SR1001 administration. However, involvement of RORα in this modulation through potential apoptotic target genes remains elusive.
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