Kardiyovasküler Hastalıklarda NLRP3 Etkinliğinin Mekanizması ve Programlanmış Hücre Ölümü: Piroptozis

Yasemin Hacanlı

doi:10.5281/zenodo.15105081

Yazarlar

Yasemin Hacanlı

DOI:

https://doi.org/10.5281/zenodo.15105081

Anahtar Kelimeler:

Piroptozis, Piroptozis ve kardiyovasküler hastalıklar, NLRP3, İnflamasom, İnflamasyon

Özet

Kardiyovasküler hastalıklar dünya genelinde meydana gelen ölümlerin ~%35’inden sorumludur. Kardiyovasküler hastalıklar hipertansiyon, diyabetik kardiyomiyopati, obezite, ateroskleroz, miyokard enfarktüsü ve kalp yetmezliği gibi kalp ve kan damarlarını olumsuz etkileyen birçok rahatsızlığı içermektedir. Kardiyovasküler hastalıkların belirtileri arasında yorgunluk, kalp atışında meydana gelen bozukluklar, solunum güçlüğü ve göğüs ağrısı gibi semptomlar bulunmaktadır. Bu hastalıkların meydana gelmesinde ve ilerlemesinde etkili olan faktörler arasında ise hiperkolesterolemi, tütün kullanımı, diyabet ve tabi ki hipertansiyon yer alır. Kalpte meydana gelen hasarlar akut kalp disfonksiyonunun oluşmasını indükleyebilir. Kalpte oluşan hasar, stereotipik bir inflamatuar yanıt izleyerek daha fazla disfonksiyon ve daha fazla mortaliteye sebep olabilir. NLRP3 inflamazomu, steril inflamasyona ve doku hasarına karşı inflamatuar cevabın merkezi bir aracısı olarak kendini göstermektedir. NLRP3 bileşenleri, kalp hasarı bulunmadığı sürece göz ardı edilebilecek seviyededir. Yapılan araştırmalarda akut miyokard enfarktüsü aşamasında NLRP3 etkinliğini ortaya koyan çalışmalar mevcuttur ve NLRP3’ün aktivasyonu piroptoziste rol oynayan kaspaz-1 enziminin de artmasına neden olmaktadır. Bu derlemede, NLRP3 inflamazomunun aktivasyonuna ve bu aktivasyonun piroptozisi nasıl etkilediğine dair yapılan çalışmalara değinilmiştir.

Referanslar

Ding P, Song Y, Yang Y, Zeng C. NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention. Front Pharmacol. 2024:15:1368835. doi: 10.3389/fphar.2024.1368835.

Cai K, Jiang H, Zou Y, Song C, Cao K, Chen S, et al. Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches. Pharmacol Res. 2024;206:107281. doi: 10.1016/j.phrs.2024.107281.

Zhang L, Feng Q, Wang T. Necrostatin‐1 protects against paraquat‐induced cardiac contractile dysfunction via RIP1‐RIP3‐MLKL‐dependent necroptosis pathway. Cardiovasc Toxicol. 2018;18(4):346‐355. doi: 10.1007/s12012-017-9441-z.

Liu S, Bi Y, Han T, Li YE, Wang Q, Wu NN, et al. The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis. Cell Discov. 2024;10(1):24. doi: 10.1038/s41421-023-00622-3.

Xiang Q, Yi X, Zhu XH, Wei X, Jiang DS. Regulated cell death in myocardial ischemia-reperfusion injury. Trends Endocrinol Metab. 2024;35(3):219-234. doi: 10.1016/j.tem.2023.10.010.

Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol. 2024;21(4):219-237. doi: 10.1038/s41569-023-00946-3.

Zheng D, Liwinski T, Elinav E. Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov. 2020:6:36. doi: 10.1038/s41421-020-0167-x. eCollection 2020.

Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128. doi: 10.1038/s41392-021-00507-5.

Broz P, Pelegrín P, Shao F. The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2020;20(3):143-157. doi: 10.1038/s41577-019-0228-2.

Wang Y, Gao W, Shi X, Ding J, Liu W, He H. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin Nature. 2017;547(7661):99-103. doi: 10.1038/nature22393.

Zhaolin Z, Guohua L, Shiyuan W, Zuo W. Role of pyroptosis in cardiovascular disease. Cell Prolif. 2019;52(2):e12563. doi: 10.1111/cpr.12563.

Abbate A, Toldo S, Marchetti C, Kron J, Tassell BWV, Dinarello CA. Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease. Circ Res. 2020;126(9):1260-1280. doi: 10.1161/CIRCRESAHA.120.315937.

Kayagaki N, Warming S, Lamkanfi M, Walle LV, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479(7371):117-21. doi: 10.1038/nature10558.

Ranson N, Kunde D, Eri R. Regulation and sensing of inflammasomes and their impact on Intestinal Health. Int J Mol Sci. 2017;18(11). doi: 10.3390/ijms18112379.

Nagata S, Tanaka M. Programmed cell death and the immune system. Nat Reviews Immunol 2017. 2017;17(5):5. doi: 10.1038/nri.2016.153.

An J, Kim SY, Yang EG, Chung HS. A fluorescence-polarization-based lipopolysaccharide-Caspase-4 Interaction Assay for the development of inhibitors. Molecules. 2022;27(8):2458. doi: 10.3390/molecules27082458.

Downs KP, Nguyen H, Dorfleutner A, Stehlik C. An overview of the non-canonical inflammasome. Mol Aspects Med. 2020:76:100924. doi: 10.1016/j.mam.2020.100924.

Ma Q. Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction. Pharmacol Rev. 2023;75(3):487-520. doi: 10.1124/pharmrev.122.000629.

Garcia ABSC, Schnur KP, Malik AB, Mo GCH. Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry. Nat Commun. 2022;13(1):52. doi: 10.1038/s41467-021-27692-9.

Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. doi: 10.1111/imr.12621.

Seropian IM, Toldo S, Tassell BWV, Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol. 2014;63(16):1593-603. doi: 10.1016/j.jacc.2014.01.014.

Wang L, Qu P, Zhao J, Chang Y. NLRP3 and downstream cytokine expression elevated in the monocytes of patients with coronary artery disease. Arch Med Sci. 2014;10(4):791-800. doi: 10.5114/aoms.2014.44871.

Toldo S, Mezzaroma E, McGeough MD, Peña CA, Marchetti C, Sonnino C. Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart. Cardiovasc Res. 2015;105(2):203-12. doi: 10.1093/cvr/cvu259.

Li X, Li F, Chu Y, Wang X, Zhang H, Hu Y, et al. NOD2 deficiency protects against cardiac remodeling after myocardial infarction in mice. Cell Physiol Biochem. 2013;32(6):1857-66. doi: 10.1159/000356618.

Mezzaroma E, Abbate A, Toldo S. The inflammasome in heart failure. Curr Opin Physiol. 2021:19:105-112. doi: 10.1016/j.cophys.2020.09.013.

Suetomi T, Willeford A, Brand CS, Cho Y, Ross RS, Miyamoto S, et al. Inflammation and NLRP3 Inflammasome Activation Initiated in Response to Pressure Overload by Ca2+/Calmodulin-Dependent Protein Kinase II δ Signaling in Cardiomyocytes Are Essential for Adverse Cardiac Remodeling. Circulation. 2018;138(22):2530-2544. doi: 10.1161/CIRCULATIONAHA.118.034621.

Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357-61. doi: 10.1038/nature08938.

Jiang M, Sun X, Liu S, Tang Y, Shi Y, Bai Y, et al. Caspase-11-gasdermin D-mediated pyroptosis is involved in the pathogenesis of atherosclerosis. Front Pharmacol. 2021:12:657486. doi: 10.3389/fphar.2021.657486.

Pappritz K, Sun X, Liu S, Tang Y, Shi Y, Bai Y, et al. Colchicine prevents disease progression in viral myocarditis via modulating the NLRP3 inflammasome in the cardiosplenic axis. Front Pharmacol. 2021:12:657486. doi: 10.1002/ehf2.13845.

Kron J, Mauro AG, Bonaventura A, Toldo S, Salloum FN, Ellenbogen KA, et al. Inflammasome formation in granulomas in cardiac sarcoidosis. Circ. Arrhythm. Circ Arrhythm Electrophysiol. 2019;12(9):e007582. doi: 10.1161/CIRCEP.119.007582.

Soliman EZ, Prineas RJ. Antihypertensive therapies and left ventricular hypertrophy. Curr Hypertens Rep. 2017;19(10):79. doi: 10.1007/s11906-017-0777-3.

Bai Y, Sun X, Chu Q, Li A, Qin Y, Li Y, et al. Caspase‐1 regulates Ang II‐induced cardiomyocyte hypertrophy via up‐regulation of IL‐1 beta. Biosci Rep. 2018;38(2):BSR20171438. doi: 10.1042/BSR20171438.

Toldo S, Marchetti C, Mauro AG, Chojnacki J, Mezzaroma E, Carbone S, et al. Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia–reperfusion in the mouse. Int J Cardiol. 2016;209:215–220. doi: 10.1016/j.ijcard.2016.02.043.

Zeng C, Duan F, Hu J, Luo B, Huang B, Lou X, et al. NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy Redox Biol. 2020:34:101523. doi: 10.1016/j.redox.2020.101523.

Marchetti C, Toldo S, Chojnacki J, Mezzaroma E, Liu K, Salloum FN, et al. Pharmacologic inhibition of the NLRP3 inflammasome preserves cardiac function after ischemic and nonischemic injury in the mouse. J Cardiovasc Pharmacol. 2015;66(1):1-8. doi: 10.1097/FJC.0000000000000247.

Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H. Inflammasome Activation of Cardiac Fibroblasts Is Essential for Myocardial Ischemia/Reperfusion Injury. Circulation. 2011;123(6):594-604. doi: 10.1161/CIRCULATIONAHA.110.982777.

Mauro AG, Mezzaroma E, Torrado J, Kundur P, Joshi P, Stroud K, et al. Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha. J Cardiovasc Pharmacol. 2017;69(3):156-160. doi: 10.1097/FJC.0000000000000452.

Hettwer J, Hinterdobler J, Miritsch B, Deutsch MA, Li X, Mauersberger C, et al. Interleukin-1β suppression dampens inflammatory leucocyte production and uptake in atherosclerosis. Cardiovasc Res. 2022;118(13):2778-2791. doi: 10.1093/cvr/cvab337.

Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128. doi: 10.1038/s41392-021-00507-5.

Dargani ZT, Singla DK. Embryonic stem cell-derived exosomes inhibit doxorubicin-induced TLR4-NLRP3-mediated cell death-pyroptosis. Am J Physiol Heart Circ Physiol. 2019;317(2):H460-H471. doi: 10.1152/ajpheart.00056.2019.