Paeonol attenuates atherosclerosis by regulating vascular smooth muscle cells apoptosis and modulating immune cells infiltration through reducing LTβR expression
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View abstract on PubMed
Summary
This summary is machine-generated.Paeonol (Pae) stabilizes vulnerable atherosclerotic plaques by inhibiting vascular smooth muscle cell (VSMC) apoptosis and immune cell infiltration via the LTβR/NIK/caspase-3 pathway. This study reveals Pae as a potential therapeutic agent for atherosclerosis.
Area Of Science
- Cardiovascular Biology
- Immunology
- Pharmacology
Background
- Atherosclerosis is a chronic inflammatory disease characterized by plaque instability, leading to adverse clinical events.
- Understanding mechanisms of plaque stabilization, particularly targeting vascular smooth muscle cell (VSMC) apoptosis and immune cell infiltration, is crucial for updated atherosclerosis treatments.
- Paeonol (Pae), a natural phenolic compound, exhibits anti-inflammatory properties, but its specific mechanisms in stabilizing atherosclerotic plaques remain unclear.
Purpose Of The Study
- To elucidate the therapeutic effects of Pae on atherosclerotic unstable plaques.
- To investigate the underlying mechanisms of Pae in inhibiting VSMC apoptosis and immune cell infiltration.
Main Methods
- Established a high-fat diet-induced atherosclerosis model in ApoE<sup>-/-</sup> mice, treated with Pae or simvastatin.
- Assessed plaque formation, lipid accumulation, and immune cell infiltration using histological and immunofluorescence techniques.
- Evaluated VSMC apoptosis via TUNEL staining and flow cytometry; analyzed LTβR/NIK/caspase-3 pathway signaling using RT-PCR and Western blotting.
Main Results
- Pae significantly inhibited atherosclerosis progression and stabilized vulnerable plaques, reducing T/B cell infiltration and VSMC apoptosis in ApoE<sup>-/-</sup> mice.
- A positive correlation was observed between T/B cell infiltration and VSMC apoptosis, with LTβR expressed on apoptotic VSMCs potentially activated by LTα<sub>1</sub>β<sub>2</sub>.
- Pae treatment decreased LTβR expression and inhibited the LTβR/NIK/caspase-3 pathway, reducing LTα<sub>1</sub>β<sub>2</sub>-stimulated VSMC apoptosis in vitro and in vivo.
Conclusions
- Inhibition of LTβR signaling is a promising therapeutic strategy for atherosclerosis, simultaneously suppressing immune cell infiltration and VSMC apoptosis.
- Pae demonstrates novel anti-atherosclerosis mechanisms by targeting the LTβR/NIK/caspase-3 pathway.
- These findings provide new insights into Pae's therapeutic potential for stabilizing vulnerable atherosclerotic plaques.
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