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Protein Inhibitor of Activated STAT3 Suppresses Oxidized LDL-induced Cell Responses during Atherosclerosis in
Rong Wang1,2, Yanjin Zhang3, Liran Xu1,2
1Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.
Abstract:
Atherosclerosis is a serious public health concern. Excessive inflammatory responses of vascular cells are considered a pivotal pathogenesis mechanism underlying atherosclerosis development. It is known that Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signalling plays an important role in atherosclerosis progression. Protein inhibitor of activated STAT3 (PIAS3) is the key negative regulator of JAK/STAT3 signalling. However, its effect on atherogenesis is unknown. Here, we observed that PIAS3 levels are reduced in atherosclerotic lesions and that PIAS3 expression decreases in conjunction with increases in interleukin-6 expression and atherosclerosis severity. Oxidized low-density lipoprotein (ox-LDL), an atherogenic stimulus, reduced PIAS3 expression, an effect that may be attributed to nitric oxide synthesis upregulation. In turn, PIAS3 overexpression effectively suppressed ox-LDL-induced inflammation, lipid accumulation and vascular smooth muscle cell proliferation. These results indicate that PIAS3 is a critical repressor of atherosclerosis progression. The findings of this study have contributed to our understanding on the pathogenesis of atherosclerosis and have provided us with a potential target through which we can inhibit atherosclerosis-related cellular responses.
Insights
Protein inhibitor of activated STAT3 (PIAS3) suppresses atherosclerosis development by reducing inflammation and cell proliferation. Lower PIAS3 levels correlate with increased disease severity, suggesting PIAS3 is a key regulator in preventing atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Atherosclerosis is a major public health issue driven by vascular cell inflammation.
- Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling is implicated in atherosclerosis progression.
- Protein inhibitor of activated STAT3 (PIAS3) negatively regulates JAK/STAT3 signaling, but its role in atherosclerosis is unclear.
Purpose of the Study:
- To investigate the role of PIAS3 in the pathogenesis of atherosclerosis.
- To determine the effect of PIAS3 on oxidized low-density lipoprotein (ox-LDL)-induced cellular responses.
Main Methods:
- Quantified PIAS3 levels in atherosclerotic lesions.
- Assessed the impact of ox-LDL on PIAS3 expression.
- Overexpressed PIAS3 to evaluate its effects on inflammation, lipid accumulation, and cell proliferation.
Main Results:
- PIAS3 levels were reduced in atherosclerotic lesions, inversely correlating with interleukin-6 and disease severity.
- Oxidized low-density lipoprotein (ox-LDL) decreased PIAS3 expression, potentially via nitric oxide synthesis.
- PIAS3 overexpression inhibited ox-LDL-induced inflammation, lipid accumulation, and vascular smooth muscle cell proliferation.
Conclusions:
- PIAS3 acts as a critical repressor of atherosclerosis progression.
- PIAS3 is a potential therapeutic target for inhibiting atherosclerosis-related cellular responses.
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