{"title":"Attenuating Atherosclerosis through Inhibition of the NF-κB/NLRP3/IL-1β Pathway-Mediated Pyroptosis in Vascular Smooth Muscle Cells (VSMCs)","authors":"Shihuan Li, Qingjie Li, Qiaofeng Zhou, Suqin Li, Siqi Wang, Qing Yao, Changhan Ouyang, Chao Liu, Mincai Li","doi":"10.1155/2024/1506083","DOIUrl":null,"url":null,"abstract":"<p><i>Objective</i>. We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway. <i>Methods and Results</i>. Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 <i>μ</i>mol/L Res. The calcium salt was detected by alizarin red S staining. Res and MCC950 downregulated the calcification, inflammatory, pyroptosis, and transcription factor-related indicators all decreased by RT-qPCR with Western blot and immunofluorescence. The results showed that Res and MCC950 refrained the calcification of VSMCs and that Res has a better effect than MCC950. Plaques and calcium salt deposits were present in the carotid region in the control group. More calcium salt deposits were evident in the plaques of the Par group by HE staining and alizarin red S staining. The calcification indexes BMP2, Runx2, and related indexes declined by immunofluorescence, which showed parthenolide-inhibited AS. The related protein expressions were consistent with the expression of the cell experiments. <i>Conclusion</i>. Our data demonstrated that inflammatory response and pyroptosis exacerbate AS and unravel the link between VSMCs and the progression of AS lesions. Res and MCC950 inhibited the calcification of VSMCs by regulating NF-<i>κ</i>B/NLRP3/IL-1<i>β</i> signaling axis. P53 can exacerbate the AS lesions by acting on NLRP3 inflammasome and pyroptosis. Our findings supported the clinical applications of Res and MCC950 in VSMCs individuals to counteract pyroptosis and AS, and P53 inhibitors also can be a potential treatment for AS.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/1506083","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/1506083","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Objective. We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway. Methods and Results. Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 μmol/L Res. The calcium salt was detected by alizarin red S staining. Res and MCC950 downregulated the calcification, inflammatory, pyroptosis, and transcription factor-related indicators all decreased by RT-qPCR with Western blot and immunofluorescence. The results showed that Res and MCC950 refrained the calcification of VSMCs and that Res has a better effect than MCC950. Plaques and calcium salt deposits were present in the carotid region in the control group. More calcium salt deposits were evident in the plaques of the Par group by HE staining and alizarin red S staining. The calcification indexes BMP2, Runx2, and related indexes declined by immunofluorescence, which showed parthenolide-inhibited AS. The related protein expressions were consistent with the expression of the cell experiments. Conclusion. Our data demonstrated that inflammatory response and pyroptosis exacerbate AS and unravel the link between VSMCs and the progression of AS lesions. Res and MCC950 inhibited the calcification of VSMCs by regulating NF-κB/NLRP3/IL-1β signaling axis. P53 can exacerbate the AS lesions by acting on NLRP3 inflammasome and pyroptosis. Our findings supported the clinical applications of Res and MCC950 in VSMCs individuals to counteract pyroptosis and AS, and P53 inhibitors also can be a potential treatment for AS.
期刊介绍:
Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged.
Subject areas include (but are by no means limited to):
Acute coronary syndrome
Arrhythmias
Atherosclerosis
Basic cardiac electrophysiology
Cardiac catheterization
Cardiac remodeling
Coagulation and thrombosis
Diabetic cardiovascular disease
Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF)
Hyperlipidemia
Hypertension
Ischemic heart disease
Vascular biology
Ventricular assist devices
Molecular cardio-biology
Myocardial regeneration
Lipoprotein metabolism
Radial artery access
Percutaneous coronary intervention
Transcatheter aortic and mitral valve replacement.