P65/NLRP3 Inflammasome Mediated Endothelial Cells Pyroptosis: A Novel Mechanism of In-Stent Restenosis
DOI:
https://doi.org/10.59958/hsf.6845Keywords:
in-stent restenosis, pyroptosis, rabbits, NLRP3 inflammasomeAbstract
Background: In-stent restenosis (ISR) is one of the key causes of ischemic events after coronary stent implantation, and endothelial cell death and inflammation are considered to be important mechanisms. Pyroptosis is a proinflammatory type of programmed cell death, the effects and underlying mechanisms of endothelial cell (EC) pyroptosis in ISR remains unclear. Method: According to our previous work, an ISR rabbit model was established. Rabbits were divided into sham operation group and stent group. Serum was collected at 0, 4, 8, and 12 weeks to detect interleukin (IL)-1β and IL-18 levels. Rabbits' vascular EC was collected to detect NLRP3, Caspase1, GSDMD and P65 expression by western blot. NLRP3 inhibitor (MCC950) and P65 inhibitor (Helenalin) were used to pretreat EC, cell viability, lactate dehydrogenase (LDH) level of supernatant and pyroptosis related protein expression were measured in different groups. Results: The serum levels of IL-1β and IL-18 gradually increased with time, and the levels at the site of stent implantation were higher than the peripheral level. EC viability decreased significantly in the stent group, and protein levels of NLRP3, caspase1 and GSDMD were higher than those in the sham group. MCC950 and P65 inhibitors can reverse these effects. Conclusions: EC pyroptosis mediated by P65/NLRP3 inflammasome axis may promote ISR, our results provide a potential intervention target for the treatment of ISR.
References
Al-Lamee RK, Nowbar AN, Francis DP. Percutaneous coronary intervention for stable coronary artery disease. Heart. 2019; 105: 11–19.
Burzotta F, Lassen JF, Banning AP, Lefèvre T, Hildick-Smith D, Chieffo A, et al. Percutaneous coronary intervention in left main coronary artery disease: the 13th consensus document from the European Bifurcation Club. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2018; 14: 112–120.
Nakamura D, Dohi T, Ishihara T, Kikuchi A, Mori N, Yokoi K, et al. Predictors and outcomes of neoatherosclerosis in patients with in-stent restenosis. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2021; 17: 489–496.
Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. Journal of the American College of Cardiology. 2014; 63: 2659–2673.
Nogourani MK, Moradi M, Khajouei AS, Farghadani M, Eshaghian A. Diagnostic value of intraluminal stent enhancement in estimating coronary in-stent restenosis. Journal of Clinical Imaging Science. 2020; 10: 12.
Pepe M, Napoli G, Carulli E, Moscarelli M, Forleo C, Nestola PL, et al. Autoimmune diseases in patients undergoing percutaneous coronary intervention: A risk factor for in-stent restenosis? Atherosclerosis. 2021; 333: 24–31.
Aoki J, Tanabe K. Mechanisms of drug-eluting stent restenosis. Cardiovascular Intervention and Therapeutics. 2021; 36: 23–29.
Wasser K, Schnaudigel S, Wohlfahrt J, Psychogios MN, Knauth M, Gröschel K. Inflammation and in-stent restenosis: the role of serum markers and stent characteristics in carotid artery stenting. PloS One. 2011; 6: e22683.
Liang H, Cui Y, Bu H, Liu H, Yan P, Cui L, et al. Value of S100A12 in predicting in-stent restenosis in patients with coronary drug-eluting stent implantation. Experimental and Therapeutic Medicine. 2020; 20: 211–218.
Araújo PV, Ribeiro MS, Dalio MB, Rocha LA, Viaro F, Dellalibera Joviliano R, et al. Interleukins and inflammatory markers in in-stent restenosis after femoral percutaneous transluminal angioplasty. Annals of Vascular Surgery. 2015; 29: 731–737.
Jiang F, Zhang X, Lu YM, Li YG, Zhou X, Wang YS. Elevated level of miR-17 along with decreased levels of TIMP-1 and IL-6 in plasma associated with the risk of in-stent restenosis. Bioscience Trends. 2019; 13: 423–429.
Liu X, Zhang R, Fu G, Sun Y, Wu J, Zhang M, et al. Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima. Cardiovascular Drugs and Therapy. 2021; 35: 915–925.
Wang J, Wang Y, Zhao Y, Zhao J, Zhang B, Xu K. EGCG Regulates Cell Apoptosis of Human Umbilical Vein Endothelial Cells Grown on 316L Stainless Steel for Stent Implantation. Drug Design, Development and Therapy. 2021; 15: 493–499.
Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduction and Targeted Therapy. 2021; 6: 128.
Luo X, Bao X, Weng X, Bai X, Feng Y, Huang J, et al. The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway. Life Sciences. 2022; 291: 120064.
Tan Y, Chen Q, Li X, Zeng Z, Xiong W, Li G, et al. Pyroptosis: a new paradigm of cell death for fighting against cancer. Journal of Experimental & Clinical Cancer Research: CR. 2021; 40: 153.
Xu YJ, Zheng L, Hu YW, Wang Q. Pyroptosis and its relationship to atherosclerosis. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2018; 476: 28–37.
He X, Fan X, Bai B, Lu N, Zhang S, Zhang L. Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis. Pharmacological Research. 2021; 165: 105447.
Wang G, Luo X, Zhang R, Chen S, Hou J, Yu B. A Novel Rabbit Model for In-Stent Neoatherosclerosis. International Heart Journal. 2019; 60: 1154–1160.
Zhang Y, Ying F, Tian X, Lei Z, Li X, Lo CY, et al. TRPM2 Promotes Atherosclerotic Progression in a Mouse Model of Atherosclerosis. Cells. 2022; 11: 1423.
Song T, Fu Y, Wang Y, Li W, Zhao J, Wang X, et al. FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree, and independently predicts in-stent restenosis risk in coronary heart disease patients underwent drug-eluting-stent PCI. BMC Cardiovascular Disorders. 2021; 21: 24.
Shlofmitz E, Iantorno M, Waksman R. Restenosis of Drug-Eluting Stents: A New Classification System Based on Disease Mechanism to Guide Treatment and State-of-the-Art Review. Circulation. Cardiovascular Interventions. 2019; 12: e007023.
Guo N, Chen F, Zhou J, Fang Y, Li H, Luo Y, et al. Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells. Journal of Cardiovascular Pharmacology. 2015; 66: 338–346.
Jiang F, Zhang X, Lu M, Li Y, Zhou X, Wang Y. Elevated level of miR-17 along with decreased levels of TIMP-1 and IL-6 in plasma associated with the risk of in-stent restenosis. Bioscience Trends. 2019; 13: 423–429.
Liu X, Zhang R, Hou J, Wu J, Zhang M, Fang S, et al. Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation. Clinical Science (London, England: 1979). 2019; 133: 869–884.
Yu J, Cui X, Zhang X, Cheng M, Cui X. Advances in the Occurrence of Pyroptosis: A Novel Role in Atherosclerosis. Current Pharmaceutical Biotechnology. 2021; 22: 1548–1558.
Jia C, Zhang J, Chen H, Zhuge Y, Chen H, Qian F, et al. Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death & Disease. 2019; 10: 778.
Olona A, Hateley C, Guerrero A, Ko JH, Johnson MR, Anand PK, et al. Cardiac glycosides cause cytotoxicity in human macrophages and ameliorate white adipose tissue homeostasis. British Journal of Pharmacology. 2022; 179: 1874–1886.
Wang F, Li C, Ding FH, Shen Y, Gao J, Liu ZH, et al. Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells. Atherosclerosis. 2017; 267: 10–18.
Shen Y, Li C, Zhang RY, Zhang Q, Shen WF, Ding FH, et al. Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells. International Journal of Cardiology. 2017; 228: 129–136.
Liu C, Wu J, Jia H, Lu C, Liu J, Li Y, et al. Oncostatin M promotes the ox-LDL-induced activation of NLRP3 inflammasomes via the NF-κB pathway in THP-1 macrophages and promotes the progression of atherosclerosis. Annals of Translational Medicine. 2022; 10: 456.
Lehrke M, Kahles F, Makowska A, Tilstam PV, Diebold S, Marx J, et al. PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner. Journal of Molecular and Cellular Cardiology. 2015; 81: 23–33.
Weng X, Luo X, Dai X, Lv Y, Zhang S, Bai X, et al. Apigenin inhibits macrophage pyroptosis through regulation of oxidative stress and the NF-κB pathway and ameliorates atherosclerosis. Phytotherapy Research: PTR. 2023; 37: 5300–5314.
Luo X, Weng X, Bao X, Bai X, Lv Y, Zhang S, et al. A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis. Redox Biology. 2022; 57: 102511.
Wang YF, Zhao LN, Geng Y, Yuan HF, Hou CY, Zhang HH, et al. Aspirin modulates succinylation of PGAM1K99 to restrict the glycolysis through NF-κB/HAT1/PGAM1 signaling in liver cancer. Acta Pharmacologica Sinica. 2023; 44: 211–220.
Nežić L, Amidžić L, Škrbić R, Gajanin R, Mandić D, Dumanović J, et al. Amelioration of Endotoxin-Induced Acute Lung Injury and Alveolar Epithelial Cells Apoptosis by Simvastatin Is Associated with Up-Regulation of Survivin/NF-κB/p65 Pathway. International Journal of Molecular Sciences. 2022; 23: 2596.
