Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review)

Global Burden of Cardiovascular Diseases and Risks 2023 Collaborators: Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factorsin 204 Countries and Territories, 1990-2023. J Am Coll Cardiol. 86:2167–2243. 2025. View Article : Google Scholar

Writing Group Members; Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després JP, et al: Executive summary: Heart disease and stroke statistics-2016 Update: A report from the american heart association. Circulation. 133:447–454. 2016. View Article : Google Scholar : PubMed/NCBI

Caldarelli M, Franza L, Cutrupi S, Menegolo M, Franceschi F, Gasbarrini A, Gambassi G and Cianci R: Inflammasomes in cardiovascular diseases: Current knowledge and future perspectives. Int J Mol Sci. 26:54392025. View Article : Google Scholar : PubMed/NCBI

Borim PA, Gatto M, Mota GAF, Meirelles ALB, Dos Santos ACC, Pagan LU, Ojopi EPB, Rodrigues EA, Souza LM, Damatto FC, et al: Nlrc4 Inflammasome expression after acute myocardial infarction in rats. Int J Mol Sci. 26:36972025. View Article : Google Scholar : PubMed/NCBI

Sun B, Xun Z, Zhou Z, Zhang N, Piao M, Li C, Li J, Li S, Zhang L, Chen X, et al: Single-cell transcriptomic analysis deciphers the inflammatory microenvironment characterized by CXCL9⁺ fibroblasts and ACKR1+ endothelial cells in immune-related myocarditis. J Transl Med. 23:5552025. View Article : Google Scholar

Aboukhater D, Morad B, Nasrallah N, Nasser SA, Sahebkar A, Kobeissy F, Boudaka A and Eid AH: Inflammation and hypertension: Underlying mechanisms and emerging understandings. J Cell Physiol. 238:1148–1159. 2023. View Article : Google Scholar : PubMed/NCBI

Tezen O, Hayıroğlu Mİ, Pay L, Yumurtaş AÇ, Keskin K, Çetin T, Dereli Ş, Kadığoğlu H, Yücedağ FF, Arter E and Dayı ŞÜ: The role of systemic immune-inflammatory index in predicting contrast-induced nephropathy in non-ST-segment elevation myocardial infarction cases. Biomark Med. 18:937–944. 2024. View Article : Google Scholar : PubMed/NCBI

Hayıroğlu Mİ and Altay S: Overlap between nutritional indices in patients with acute coronary syndrome: A focus on albumin. Balkan Med J. 41:324–325. 2024.

Lian Y, Lai X, Wu C, Wang L, Shang J, Zhang H, Jia S, Xing W and Liu H: The roles of neutrophils in cardiovascular diseases. Front Cardiovasc Med. 12:15261702025. View Article : Google Scholar : PubMed/NCBI

Döring Y, Libby P and Soehnlein O: Neutrophil extracellular traps participate in cardiovascular diseases: Recent experimental and clinical insights. Circ Res. 126:1228–1241. 2020. View Article : Google Scholar : PubMed/NCBI

Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y and Zychlinsky A: Neutrophil extracellular traps kill bacteria. Science. 303:1532–1535. 2004. View Article : Google Scholar : PubMed/NCBI

Dwyer M, Shan Q, D'Ortona S, Maurer R, Mitchell R, Olesen H, Thiel S, Huebner J and Gadjeva M: Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor. J Innate Immun. 6:765–779. 2014. View Article : Google Scholar : PubMed/NCBI

Petretto A, Bruschi M, Pratesi F, Croia C, Candiano G, Ghiggeri G and Migliorini P: Neutrophil extracellular traps (NET) induced by different stimuli: A comparative proteomic analysis. PLoS One. 14:e02189462019. View Article : Google Scholar : PubMed/NCBI

Wang H, Kim SJ, Lei Y, Wang S, Wang H, Huang H, Zhang H and Tsung A: Neutrophil extracellular traps in homeostasis and disease. Signal Transduct Target Ther. 9:2352024. View Article : Google Scholar : PubMed/NCBI

Hakkim A, Fuchs TA, Martinez NE, Hess S, Prinz H, Zychlinsky A and Waldmann H: Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nat Chem Biol. 7:75–77. 2011. View Article : Google Scholar

Vorobjeva N, Dagil Y, Pashenkov M, Pinegin B and Chernyak B: Protein kinase C isoforms mediate the formation of neutrophil extracellular traps. Int Immunopharmacol. 114:1094482023. View Article : Google Scholar

Hidalgo A, Libby P, Soehnlein O, Aramburu IV, Papayannopoulos V and Silvestre-Roig C: Neutrophil extracellular traps: From physiology to pathology. Cardiovasc Res. 118:2737–2753. 2022. View Article : Google Scholar :

Vorobjeva NV and Chernyak BV: NETosis: Molecular mechanisms, role in physiology and pathology. Biochemistry (Mosc). 85:1178–1190. 2020. View Article : Google Scholar : PubMed/NCBI

Herre M, Cedervall J, Mackman N and Olsson AK: Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases. Physiol Rev. 103:277–312. 2023. View Article : Google Scholar

Liang C, Lian N and Li M: The emerging role of neutrophil extracellular traps in fungal infection. Front Cell Infect Microbiol. 12:9008952022. View Article : Google Scholar : PubMed/NCBI

Douda DN, Khan MA, Grasemann H and Palaniyar N: SK3 channel and mitochondrial ROS mediate NADPH oxidaseindependent NETosis induced by calcium influx. Proc Natl Acad Sci USA. 112:2817–2822. 2015. View Article : Google Scholar

Warnatsch A, Ioannou M, Wang Q and Papayannopoulos V: Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science. 349:316–320. 2015. View Article : Google Scholar : PubMed/NCBI

Sorci-Thomas MG and Thomas MJ: Microdomains, inflammation, and atherosclerosis. Circ Res. 118:679–691. 2016. View Article : Google Scholar : PubMed/NCBI

Wang L, Zhou X, Yin Y, Mai Y, Wang D and Zhang X: Hyperglycemia induces neutrophil extracellular traps formation through an NADPH Oxidase-dependent pathway in diabetic retinopathy. Front Immunol. 9:30762019. View Article : Google Scholar : PubMed/NCBI

Kim SW and Lee JK: Role of HMGB1 in the interplay between NETosis and Thrombosis in ischemic stroke: A review. Cells. 9:17942020. View Article : Google Scholar : PubMed/NCBI

McDonald B, Davis RP, Kim SJ, Tse M, Esmon CT, Kolaczkowska E and Jenne CN: Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 129:1357–1367. 2017. View Article : Google Scholar : PubMed/NCBI

Iba T, Levi M and Levy JH: Intracellular communication and immunothrombosis in sepsis. J Thromb Haemost. 20:2475–2484. 2022. View Article : Google Scholar : PubMed/NCBI

Patel P, Michael JV, Naik UP and McKenzie SE: Platelet FcγRIIA in immunity and thrombosis: Adaptive immunothrombosis. J Thromb Haemost. 19:1149–1160. 2021. View Article : Google Scholar : PubMed/NCBI

Molinaro R, Yu M, Sausen G, Bichsel CA, Corbo C, Folco EJ, Lee GY, Liu Y, Tesmenitsky Y, Shvartz E, et al: Targeted delivery of protein arginine deiminase-4 inhibitors to limit arterial intimal NETosis and preserve endothelial integrity. Cardiovasc Res. 117:2652–2663. 2021.PubMed/NCBI

An Z, Li J, Yu J, Wang X, Gao H, Zhang W, Wei Z, Zhang J, Zhang Y, Zhao J and Liang X: Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-κB signaling in macrophages. Cell Cycle. 18:2928–2938. 2019. View Article : Google Scholar : PubMed/NCBI

Dabravolski SA, Bukrinsky MI, Utkina AS, Ravani AL, Sukhorukov VN and Orekhov AN: Exploring neutrophil extracellular traps in cardiovascular pathologies: The impact of lipid profiles, PAD4, and radiation. Biocell. 49:931–959. 2025. View Article : Google Scholar : PubMed/NCBI

Ross EA, Devitt A and Johnson JR: Macrophages: The Good, the bad, and the gluttony. Front Immunol. 12:7081862021. View Article : Google Scholar : PubMed/NCBI

Davies LC, Jenkins SJ, Allen JE and Taylor PR: Tissue-resident macrophages. Nat Immunol. 14:986–995. 2013. View Article : Google Scholar : PubMed/NCBI

Wynn TA and Vannella KM: Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 44:450–462. 2016. View Article : Google Scholar : PubMed/NCBI

Yunna C, Mengru H, Lei W and Weidong C: Macrophage M1/M2 polarization. Eur J Pharmacol. 877:1730902020. View Article : Google Scholar : PubMed/NCBI

Tian H, Xiong Y, Zhan J, Lu Z, Zhang Y, Leng Y, Huang Q and Xia Z: Inhibition of Macrophage ARID3A alleviates myocardial ischemia-reperfusion injury after heart transplantation by reducing THBS1/CD47 Signaling-mediated neutrophil extracellular traps formation. Adv Sci (Weinh). 12:e099522025. View Article : Google Scholar : PubMed/NCBI

Ye H, Yang Q, Guo H, Wang X, Cheng L, Han B, Hong M, Ma F, Li M, Wu X, et al: Internalisation of neutrophils extracellular traps by macrophages aggravate rheumatoid arthritis via Rab5a. RMD Open. 10:e0038472024. View Article : Google Scholar : PubMed/NCBI

Sano M, Maejima Y, Nakagama S, Shiheido-Watanabe Y, Tamura N, Hirao K, Hirao K, Isobe M and Sasano T: Neutrophil extracellular traps-mediated Beclin-1 suppression aggravates atherosclerosis by inhibiting macrophage autophagy. Front Cell Dev Biol. 10:8761472022. View Article : Google Scholar : PubMed/NCBI

Conforti A, Wahlers T and Paunel-Görgülü A: Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages. PLoS One. 16:e02598942021. View Article : Google Scholar : PubMed/NCBI

Hofbauer TM, Ondracek AS, Mangold A, Scherz T, Nechvile J, Seidl V, Brostjan C and Lang IM: Neutrophil extracellular traps induce MCP-1 at the culprit site in ST-Segment elevation myocardial infarction. Front Cell Dev Biol. 8:5641692020. View Article : Google Scholar : PubMed/NCBI

Mangold A, Hofbauer TM, Ondracek AS, Artner T, Scherz T, Speidl WS, Krychtiuk KA, Sadushi-Kolici R, Jakowitsch J and Lang IM: Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients. Sci Rep. 9:163042019. View Article : Google Scholar : PubMed/NCBI

Folco EJ, Mawson TL, Vromman A, Bernardes-Souza B, Franck G, Persson O, Nakamura M, Newton G, Luscinskas FW and Libby P: Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through Interleukin-1α and cathepsin G. Arterioscler Thromb Vasc Biol. 38:1901–1912. 2018. View Article : Google Scholar : PubMed/NCBI

Aldabbous L, Abdul-Salam V, McKinnon T, Duluc L, Pepke-Zaba J, Southwood M, Ainscough AJ, Hadinnapola C, Wilkins MR, Toshner M and Wojciak-Stothard B: Neutrophil extracellular traps promote angiogenesis: Evidence from vascular pathology in pulmonary hypertension. Arterioscler Thromb Vasc Biol. 36:2078–2087. 2016. View Article : Google Scholar : PubMed/NCBI

An Y, Geng K, Wang HY, Wan SR, Ma XM, Long Y, Xu Y and Jiang ZZ: Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes. Cell Commun Signal. 21:3652023. View Article : Google Scholar : PubMed/NCBI

Mou J, Chen Y, Zhu X, Xu B, Wang M, Xie J, Lin T, Gu Q, Wu Q, Che Z, et al: Emerging role of the cGAS-STING pathway in cardiovascular diseases: Biologic function, mechanisms and targeted therapy. Mol Med. 31:2182025. View Article : Google Scholar : PubMed/NCBI

Zhu S, Yu Y, Qu M, Qiu Z, Zhang H, Miao C and Guo K: Neutrophil extracellular traps contribute to immunothrombosis formation via the STING pathway in sepsis-associated lung injury. Cell Death Discov. 9:3152023. View Article : Google Scholar : PubMed/NCBI

Badimon L and Vilahur G: Thrombosis formation on atherosclerotic lesions and plaque rupture. J Intern Med. 276:618–632. 2014. View Article : Google Scholar : PubMed/NCBI

Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M and Wagner DD: P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 126:242–246. 2015. View Article : Google Scholar : PubMed/NCBI

Constantinescu-Bercu A, Grassi L, Frontini M, Salles-Crawley II, Woollard K and Crawley JT: Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2. Elife. 9:e533532020. View Article : Google Scholar

Mussbacher M, Salzmann M, Brostjan C, Hoesel B, Schoergenhofer C, Datler H, Hohensinner P, Basílio J, Petzelbauer P, Assinger A and Schmid JA: Cell Type-Specific roles of NF-κB linking inflammation and thrombosis. Front Immunol. 10:852019. View Article : Google Scholar

Su M, Chen C, Li S, Li M, Zeng Z, Zhang Y, Xia L, Li X, Zheng D, Lin Q, et al: Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nat Cardiovasc Res. 1:732–747. 2022. View Article : Google Scholar : PubMed/NCBI

Zhang W, Zhang Y, Han L, Bo T, Qi Z, Zhong H, Xu H, Hu L, Chen S and Zhang S: Double-stranded DNA enhances platelet activation, thrombosis, and myocardial injury via cyclic GMP-AMP synthase. Cardiovasc Res. 121:353–366. 2025. View Article : Google Scholar

Tallquist MD: Cardiac fibroblast diversity. Annu Rev Physiol. 82:63–78. 2020. View Article : Google Scholar : PubMed/NCBI

Ong CH, Tham CL, Harith HH, Firdaus N and Israf DA: TGF-β-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies. Eur J Pharmacol. 911:1745102021. View Article : Google Scholar

Schlittler M, Pramstaller PP, Rossini A and De Bortoli M: Myocardial fibrosis in hypertrophic cardiomyopathy: A perspective from fibroblasts. Int J Mol Sci. 24:148452023. View Article : Google Scholar : PubMed/NCBI

Frangogiannis N: Transforming growth factor-β in tissue fibrosis. J Exp Med. 217:e201901032020. View Article : Google Scholar

Kuwahara F, Kai H, Tokuda K, Kai M, Takeshita A, Egashira K and Imaizumi T: Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circulation. 106:130–135. 2002. View Article : Google Scholar : PubMed/NCBI

Eghbalzadeh K, Georgi L, Louis T, Zhao H, Keser U, Weber C, Mollenhauer M, Conforti A, Wahlers T and Paunel-Görgülü A: Compromised Anti-inflammatory action of neutrophil extracellular traps in PAD4-deficient mice contributes to aggravated acute inflammation after myocardial infarction. Front Immunol. 10:23132019. View Article : Google Scholar : PubMed/NCBI

He L, Liu R, Yue H, Zhu G, Fu L, Chen H, Guo Y and Qin C: NETs promote pathogenic cardiac fibrosis and participate in ventricular aneurysm formation after ischemia injury through the facilitation of perivascular fibrosis. Biochem Biophys Res Commun. 583:154–161. 2021. View Article : Google Scholar : PubMed/NCBI

Hara A and Tallquist MD: Fibroblast and immune cell Cross-Talk in cardiac fibrosis. Curr Cardiol Rep. 25:485–493. 2023. View Article : Google Scholar : PubMed/NCBI

Venkatachalam K, Venkatesan B, Valente AJ, Melby PC, Nandish S, Reusch JE, Clark RA and Chandrasekar B: WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-alpha (TNF-alpha)-stimulated cardiac fibroblast proliferation but inhibits TNF-alpha-induced cardiomyocyte death. J Biol Chem. 284:14414–14427. 2009. View Article : Google Scholar : PubMed/NCBI

Leicht M, Briest W and Zimmer HG: Regulation of norepinephrine-induced proliferation in cardiac fibroblasts by interleukin-6 and p42/p44 mitogen activated protein kinase. Mol Cell Biochem. 243:65–72. 2003. View Article : Google Scholar : PubMed/NCBI

Siwik DA, Chang DL and Colucci WS: Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro. Circ Res. 86:1259–1265. 2000. View Article : Google Scholar : PubMed/NCBI

Mir SA, Chatterjee A, Mitra A, Pathak K, Mahata SK and Sarkar S: Inhibition of signal transducer and activator of transcription 3 (STAT3) attenuates interleukin-6 (IL-6)-induced collagen synthesis and resultant hypertrophy in rat heart. J Biol Chem. 287:2666–2677. 2012. View Article : Google Scholar

Xu Y, Ren Y, Zou W, Wang M, Ye X and Shen W: Neutrophil extracellular traps aggravate uremic cardiomyopathy by inducing myocardial fibroblast pyroptosis. Sci Rep. 15:175092025. View Article : Google Scholar : PubMed/NCBI

Akiyama M, Zeisbrich M, Ibrahim N, Ohtsuki S, Berry GJ, Hwang PH, Goronzy JJ and Weyand CM: Neutrophil extracellular traps induce Tissue-invasive monocytes in granulomatosis with polyangiitis. Front Immunol. 10:26172019. View Article : Google Scholar : PubMed/NCBI

Piera-Velazquez S, Li Z and Jimenez SA: Role of endothelial-mesenchymal transition (EndoMT) in the pathogenesis of fibrotic disorders. Am J Pathol. 179:1074–1080. 2011. View Article : Google Scholar : PubMed/NCBI

Pieterse E, Rother N, Garsen M, Hofstra JM, Satchell SC, Hoffmann M, Loeven MA, Knaapen HK, van der Heijden OWH, Berden JHM, et al: Neutrophil Extracellular traps drive Endothelial-to-Mesenchymal transition. Arterioscler Thromb Vasc Biol. 37:1371–1379. 2017. View Article : Google Scholar : PubMed/NCBI

Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, Wrobleski SK, Wakefield TW, Hartwig JH and Wagner DD: Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 107:15880–15885. 2010. View Article : Google Scholar : PubMed/NCBI

Zhang YS, Davoudi F, Walch P, Manbachi A, Luo X, Dell'Erba V, Miri AK, Albadawi H, Arneri A, Li X, et al: Bioprinted thrombosis-on-a-chip. Lab Chip. 16:4097–4105. 2016. View Article : Google Scholar : PubMed/NCBI

Borensztajn K, Stiekema J, Nijmeijer S, Reitsma PH, Peppelenbosch MP and Spek CA: Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol. 172:309–320. 2008. View Article : Google Scholar : PubMed/NCBI

Mangold A, Alias S, Scherz T, Hofbauer M, Jakowitsch J, Panzenböck A, Simon D, Laimer D, Bangert C, Kammerlander A, et al: Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res. 116:1182–1192. 2015. View Article : Google Scholar

Mangold A, Ondracek AS, Hofbauer TM, Scherz T, Artner T, Panagiotides N, Beitzke D, Ruzicka G, Nistler S, Wohlschläger-Krenn E, et al: Culprit site extracellular DNA and microvascular obstruction in ST-elevation myocardial infarction. Cardiovasc Res. 118:2006–2017. 2022. View Article : Google Scholar

Helseth R, Shetelig C, Andersen GØ, Langseth MS, Limalanathan S, Opstad TB, Arnesen H, Hoffmann P, Eritsland J and Seljeflot I: Neutrophil extracellular trap components associate with infarct size, ventricular function, and clinical outcome in STEMI. Mediators Inflamm. 2019:78164912019. View Article : Google Scholar : PubMed/NCBI

Hofbauer TM, Mangold A, Scherz T, Seidl V, Panzenböck A, Ondracek AS, Müller J, Schneider M, Binder T, Hell L and Lang IM: Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction. Basic Res Cardiol. 114:332019. View Article : Google Scholar : PubMed/NCBI

Zhang X, Song H, Liu D, Cai Y, Liu Z, Zhang X, Zhao X, Zhang Y, Jing Q, Yan C and Han Y: S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis. Nat Commun. 16:17462025. View Article : Google Scholar : PubMed/NCBI

Wei X, Zou S, Xie Z, Wang Z, Huang N, Cen Z, Hao Y, Zhang C, Chen Z, Zhao F, et al: EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)-mediated macrophage polarization. Cardiovasc Res. 118:2179–2195. 2022. View Article : Google Scholar

Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA and Maseri A: Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation. 96:1180–1184. 1997. View Article : Google Scholar : PubMed/NCBI

Arroyo AB, de Los Reyes-García AM, Rivera-Caravaca JM, Valledor P, García-Barberá N, Roldán V, Vicente V, Martínez C and González-Conejero R: MiR-146a regulates neutrophil extracellular trap formation that predicts adverse cardiovascular events in patients with atrial fibrillation. Arterioscler Thromb Vasc Biol. 38:892–902. 2018. View Article : Google Scholar : PubMed/NCBI

He L, Liu R, Yue H, Zhang X, Pan X, Sun Y, Shi J, Zhu G, Qin C and Guo Y: Interaction between neutrophil extracellular traps and cardiomyocytes contributes to atrial fibrillation progression. Signal Transduct Target Ther. 8:2792023. View Article : Google Scholar : PubMed/NCBI

Meng S, Huang T, Zhou Z, Yu L and Wang H: Chronic mild stress exacerbates atrial fibrillation and neutrophil extracellular traps formation through S100A8/A9 signaling. Signal Transduct Target Ther. 10:1082025. View Article : Google Scholar : PubMed/NCBI

Carai P, González LF, Van Bruggen S, Spalart V, De Giorgio D, Geuens N, Martinod K, Jones EAV and Heymans S: Neutrophil inhibition improves acute inflammation in a murine model of viral myocarditis. Cardiovasc Res. 118:3331–3345. 2023. View Article : Google Scholar :

Wang Y, Chen J, Yu S, Yu Y, Yu Y, Shi H, Liu X, Chen Z, Li M, Chen R and Ge J: Neutrophil CAPNS1 regulates cardiac inflammation and injury by promoting NETosis in CVB3-induced myocarditis. Free Radic Biol Med. 248:500–515. 2026. View Article : Google Scholar : PubMed/NCBI

Liu X, Li M, Chen Z, Yu Y, Shi H, Yu Y, Wang Y, Chen R and Ge J: Mitochondrial calpain-1 activates NLRP3 inflammasome by cleaving ATP5A1 and inducing mitochondrial ROS in CVB3-induced myocarditis. Basic Res Cardio. 117:402022. View Article : Google Scholar

Li K, Song LL, Ji DJ, Zhao HQ and Wang HP: Correlation between the level of peripheral blood neutrophil extracellular trap nets and T cell expression and prognosis in patients with infective endocarditis. J Mod Lab Med. 37:183–187. 2022.In China.

Jung CJ, Yeh CY, Hsu RB, Lee CM, Shun CT and Chia JS: Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets. Circulation. 131:571–581. 2015. View Article : Google Scholar

Hsu CC, Chuang YC, Hsu RB, Chen JW, Chia JS, Shih YH, Kuo YM and Jung CJ: Streptococcus gordonii type VII secretion system substrate EsxA induces neutrophil extracellular trap formation in infective endocarditis. Sci Rep. 15:437082025. View Article : Google Scholar : PubMed/NCBI

Hsu CC, Hsu RB, Ohniwa RL, Chen JW, Yuan CT, Chia JS and Jung CJ: Neutrophil extracellular traps enhance Staphylococcus aureus vegetation formation through interaction with platelets in infective endocarditis. Thromb Haemost. 119:786–796. 2019. View Article : Google Scholar : PubMed/NCBI

Appelgren D, Dahle C, Knopf J, Bilyy R, Vovk V, Sundgren PC, Bengtsson AA, Wetterö J, Muñoz LE, Herrmann M, et al: Active NET formation in Libman-Sacks endocarditis without antiphospholipid antibodies: A dramatic onset of systemic lupus erythematosus. Autoimmunity. 51:310–318. 2018. View Article : Google Scholar : PubMed/NCBI

Ziaeian B and Fonarow GC: Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 13:368–378. 2016. View Article : Google Scholar : PubMed/NCBI

Mann DL: Inflammatory mediators and the failing heart: Past, present, and the foreseeable future. Circ Res. 91:988–998. 2002. View Article : Google Scholar : PubMed/NCBI

Ichimura S, Misaka T, Ogawara R, Tomita Y, Anzai F, Sato Y, Miura S, Yokokawa T, Sato T, Oikawa M, et al: Neutrophil extracellular traps in myocardial tissue drive cardiac dysfunction and adverse outcomes in patients with heart failure with dilated cardiomyopathy. Circ Heart Fail. 17:e0110572024. View Article : Google Scholar : PubMed/NCBI

Liu F and Zhai Q: Expression level of neutrophil extracellular traps in peripheral blood of patients with chronic heart failure complicated with venous thrombosis and its clinical significance. J Cardiothorac Surg. 19:1292024. View Article : Google Scholar : PubMed/NCBI

Tang X, Wang P, Zhang R, Watanabe I, Chang E, Vinayachandran V, Nayak L, Lapping S, Liao S, Madera A, et al: KLF2 regulates neutrophil activation and thrombosis in cardiac hypertrophy and heart failure progression. J Clin Invest. 132:e1471912022. View Article : Google Scholar :

Zhang XL, Wang TY, Chen Z, Wang HW, Yin Y, Wang L, Wang Y, Xu B and Xu W: HMGB1-promoted neutrophil extracellular traps contribute to cardiac diastolic dysfunction in mice. J Am Heart Assoc. 11:e0238002022. View Article : Google Scholar : PubMed/NCBI

Mang G, Chen J, Sun P, Ma R, Du J, Wang X, Cui J, Yang M, Tong Z, Yan X, et al: Von Willebrand factor exacerbates heart failure through formation of neutrophil extracellular traps. Eur Heart J. 45:3853–3867. 2024. View Article : Google Scholar : PubMed/NCBI

Zhao M, Zheng Z, Yin Z, Zhang J, Peng S, Liu J, Pan W, Wei C, Xu Y, Qin JJ, et al: DEL-1 deficiency aggravates pressure overload-induced heart failure by promoting neutrophil infiltration and neutrophil extracellular traps formation. Biochem Pharmacol. 218:1159122023. View Article : Google Scholar : PubMed/NCBI

Libby P: Inflammation in atherosclerosis. Nature. 420:868–874. 2002. View Article : Google Scholar : PubMed/NCBI

Megens RT, Vijayan S, Lievens D, Döring Y, van Zandvoort MA, Grommes J, Weber C and Soehnlein O: Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Haemost. 107:597–598. 2012. View Article : Google Scholar : PubMed/NCBI

Wang Y, Yang M, Xu Y, Yan S, Jin E and Li X: Neutrophil extracellular trap burden correlates with the stenosis of coronary atherosclerosis. PeerJ. 11:e154712023. View Article : Google Scholar : PubMed/NCBI

Zhu Y, Wang T, Yang Y, Wang Z, Chen X, Wang L, Niu R, Sun Z, Zhang C, Luo Y, et al: Low shear stress exacerbates atherosclerosis by inducing the generation of neutrophil extracellular traps via Piezo1-mediated mechanosensation. Atherosclerosis. 391:1174732024. View Article : Google Scholar : PubMed/NCBI

Zhang YG, Song Y, Guo XL, Miao RY, Fu YQ, Miao CF and Zhang C: Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis. Cell Cycle. 18:2674–2684. 2019. View Article : Google Scholar : PubMed/NCBI

Chen L, Hu L, Li Q, Ma J and Li H: Exosome-encapsulated miR-505 from ox-LDL-treated vascular endothelial cells aggravates atherosclerosis by inducing NET formation. Acta Biochim Biophys Sin (Shanghai). 51:1233–1241. 2019. View Article : Google Scholar : PubMed/NCBI

Han H, Liu C, Li M, Wang J, Liu YS, Zhou Y, Li ZC, Hu R, Li ZH, Wang RM, et al: Increased intracellular Cl⁻ concentration mediates neutrophil extracellular traps formation in atherosclerotic cardiovascular diseases. Acta Pharmacol Sin. 43:2848–2861. 2022. View Article : Google Scholar : PubMed/NCBI

Wang Y, Wang W, Wang N, Tall AR and Tabas I: Mitochondrial oxidative stress promotes atherosclerosis and neutrophil extracellular traps in aged mice. Arterioscler Thromb Vasc Biol. 37:e99–e107. 2017. View Article : Google Scholar : PubMed/NCBI

Dhawan UK, Bhattacharya P, Narayanan S, Manickam V, Aggarwal A and Subramanian M: Hypercholesterolemia impairs clearance of neutrophil extracellular traps and promotes inflammation and atherosclerotic plaque progression. Arterioscler Thromb Vasc Biol. 41:2598–2615. 2021. View Article : Google Scholar : PubMed/NCBI

Dhawan UK, Vartak T, Englert H, Russo S, Vasconcellos LRC, Singhal A, Chakraborty R, Bhagat KK, McDonnell C, Connolly M, et al: Macrophage DNases limit neutrophil extracellular trap-mediated defective efferocytosis in atherosclerosis. Circ Res. 137:1255–1275. 2025. View Article : Google Scholar : PubMed/NCBI

Josefs T, Barrett TJ, Brown EJ, Quezada A, Wu X, Voisin M, Amengual J and Fisher EA: Neutrophil extracellular traps promote macrophage inflammation and impair atherosclerosis resolution in diabetic mice. JCI Insight. 5:e1347962020. View Article : Google Scholar : PubMed/NCBI

Yang M, Chen Q, Mei L, Wen G, An W, Zhou X, Niu K, Liu C, Ren M, Sun K, et al: Neutrophil elastase promotes neointimal hyperplasia by targeting toll-like receptor 4 (TLR4)-NF-κB signalling. Br J Pharmacol. 178:4048–4068. 2021. View Article : Google Scholar : PubMed/NCBI

Schumski A, Ortega-Gómez A, Wichapong K, Winter C, Lemnitzer P, Viola JR, Pinilla-Vera M, Folco E, Solis-Mezarino V, Völker-Albert M, et al: Endotoxinemia accelerates atherosclerosis through electrostatic Charge-mediated monocyte adhesion. Circulation. 143:254–266. 2021. View Article : Google Scholar

Ma X, Zhao X, Yang Y, Yan J, Shi X, Wu H, Liu Y and Dai M: Paeonol inhibits NETs-mediated foam cell inflammation through the CitH3/NLRP3/caspase-1 signaling pathway in atherosclerosis. Int Immunopharmacol. 151:1143402025. View Article : Google Scholar : PubMed/NCBI

Charkiewicz AE, Garley M, Ratajczak-Wrona W, Nowak K, Jabłońska E, Maślach D and Omeljaniuk WJ: Profile of new vascular damage biomarkers in middle-aged men with arterial hypertension. Adv Med Sci. 66:185–191. 2021. View Article : Google Scholar : PubMed/NCBI

Krishnan J, Hennen EM, Ao M, Kirabo A, Ahmad T, de la Visitación N and Patrick DM: NETosis drives blood pressure elevation and vascular dysfunction in hypertension. Circ Res. 134:1483–1494. 2024. View Article : Google Scholar : PubMed/NCBI

Chrysanthopoulou A, Gkaliagkousi E, Lazaridis A, Arelaki S, Pateinakis P, Ntinopoulou M, Mitsios A, Antoniadou C, Argyriou C, Georgiadis GS, et al: Angiotensin II triggers release of neutrophil extracellular traps, linking thromboinflammation with essential hypertension. JCI Insight. 6:e1486682021. View Article : Google Scholar : PubMed/NCBI

Krishnan J, de la Visitación N, Hennen EM, Amarnath V, Harrison DG and Patrick DM: IsoLGs (Isolevuglandins) drive neutrophil migration in hypertension and are essential for the formation of neutrophil extracellular traps. Hypertension. 79:1644–1655. 2022. View Article : Google Scholar : PubMed/NCBI

Fang X, Ma L, Wang Y, Ren F, Yu Y, Yuan Z, Wei H, Zhang H and Sun Y: Neutrophil extracellular traps accelerate vascular smooth muscle cell proliferation via Akt/CDKN1b/TK1 accompanying with the occurrence of hypertension. J Hypertens. 40:2045–2057. 2022. View Article : Google Scholar : PubMed/NCBI

Tu Q, Gong X, Yuan X, Tang Y, Huang R, Jiang Q and Li W: NETs drive myocardial fibrosis in hypertension via an NF-κB/ferroptosis axis. Front Immunol. 16:17127862026. View Article : Google Scholar

Nordon IM, Hinchliffe RJ, Loftus IM and Thompson MM: Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat Rev Cardio. 8:92–102. 2011. View Article : Google Scholar

Meher AK, Spinosa M, Davis JP, Pope N, Laubach VE, Su G, Serbulea V, Leitinger N, Ailawadi G and Upchurch GR Jr: Novel role of IL (Interleukin)-1β in neutrophil extracellular trap formation and abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 38:843–853. 2018. View Article : Google Scholar : PubMed/NCBI

Wang H, Zhang R, Jia X, Gao S, Gao T, Fan K, Li Y, Wang S, Qiao M, Yan S, et al: Highly sensitive magnetic particle imaging of abdominal aortic aneurysm NETosis with anti-Ly6G iron oxide nanoparticles. Cell Death Discov. 10:3952024. View Article : Google Scholar : PubMed/NCBI

Xiong Y, Liu S, Liu Y, Zhao J, Sun J, Li Y, Pan B and Wang W: PI3Kγ promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm. JCI Insight. 9:e1832372024. View Article : Google Scholar

Tian Z, Zhang Y, Zheng Z, Zhang M, Zhang T, Jin J, Zhang X, Yao G, Kong D, Zhang C, et al: Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation. Cell Host Microbe. 30:1450–1463. 2022. View Article : Google Scholar : PubMed/NCBI

Chen L, Liu Y, Wang Z, Zhang L, Xu Y, Li Y, Zhang L, Wang G, Yang S and Xue G: Mesenchymal stem cell-derived extracellular vesicles protect against abdominal aortic aneurysm formation by inhibiting NET-induced ferroptosis. Exp Mol Med. 55:939–951. 2023. View Article : Google Scholar : PubMed/NCBI

Qi Y, Chen L, Ding S, Shen X, Wang Z, Qi H and Yang S: Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione. Free Radic Biol Med. 221:215–224. 2024. View Article : Google Scholar : PubMed/NCBI

Yang S, Chen L, Wang Z, Chen J, Ni Q, Guo X, Liu W, Lv L and Xue G: Neutrophil extracellular traps induce abdominal aortic aneurysm formation by promoting the synthetic and proinflammatory smooth muscle cell phenotype via Hippo-YAP pathway. Transl Res. 255:85–96. 2023. View Article : Google Scholar

Wei M, Wang X, Song Y, Zhu D, Qi D, Jiao S, Xie G, Liu Y, Yu B, Du J, et al: Inhibition of peptidyl arginine deiminase 4-Dependent neutrophil extracellular trap formation reduces angiotensin II-Induced abdominal aortic aneurysm rupture in mice. Front Cardiovasc Med. 8:6766122021. View Article : Google Scholar : PubMed/NCBI

Yan H, Zhou HF, Akk A, Hu Y, Springer LE, Ennis TL and Pham CTN: Neutrophil proteases promote experimental abdominal aortic aneurysm via extracellular trap release and plasmacytoid dendritic cell activation. Arterioscler Thromb Vasc Biol. 36:1660–1669. 2016. View Article : Google Scholar : PubMed/NCBI

Goody PR, Hosen MR, Christmann D, Niepmann ST, Zietzer A, Adam M, Bönner F, Zimmer S, Nickenig G and Jansen F: Aortic valve stenosis: From basic mechanisms to novel therapeutic targets. Arterioscler Thromb Vasc Biol. 40:885–900. 2020. View Article : Google Scholar : PubMed/NCBI

Dweck MR, Khaw HJ, Sng GK, Luo EL, Baird A, Williams MC, Makiello P, Mirsadraee S, Joshi NV, van Beek EJ, et al: Aortic stenosis, atherosclerosis, and skeletal bone: Is there a common link with calcification and inflammation? Eur Heart J. 34:1567–1574. 2013. View Article : Google Scholar : PubMed/NCBI

Aikawa E and Libby P: A Rock and a hard place: Chiseling away at the multiple mechanisms of aortic stenosis. Circulation. 135:1951–1955. 2017. View Article : Google Scholar : PubMed/NCBI

Kopytek M, Kolasa-Trela R, Ząbczyk M, Undas A and Natorska J: NETosis is associated with the severity of aortic stenosis: Links with inflammation. Int J Cardiol. 286:121–126. 2019. View Article : Google Scholar : PubMed/NCBI

Mangold A, Ondracek AS, Hofbauer TM, Artner T, Nechvile J, Panagiotides NG, Mirna M, Hammerer M, Fejzic D, Hoppe U, et al: Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement. Eur J Clin Invest. 51:e135952021. View Article : Google Scholar : PubMed/NCBI

Mohty D, Pibarot P, Després JP, Côté C, Arsenault B, Cartier A, Cosnay P, Couture C and Mathieu P: Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arterioscler Thromb Vasc Biol. 28:187–193. 2008. View Article : Google Scholar

Awasthi D, Nagarkoti S, Kumar A, Dubey M, Singh AK, Pathak P, Chandra T, Barthwal MK and Dikshit M: Oxidized LDL induced extracellular trap formation in human neutrophils via TLR-PKC-IRAK-MAPK and NADPH-oxidase activation. Free Radic Biol Med. 93:190–203. 2016. View Article : Google Scholar : PubMed/NCBI

Akahori H, Tsujino T, Masuyama T and Ishihara M: Mechanisms of aortic stenosis. J Cardiol. 71:215–220. 2018. View Article : Google Scholar

Cotter AB, Costa C, Alhajj N, da Silva JP, Grenha A, Mukherjee S, O'Reilly NJ and Padrela L: Inhalable dry powder formulations of the commercialised form of Deoxyribonuclease I-a dried alternative for the treatment of cystic fibrosis. Eur J Pharm Sci. 220:1074632026. View Article : Google Scholar

Roe T, Talbot T, Terrington I, Johal J, Kemp I, Saeed K, Webb E, Cusack R, Grocott MPW and Dushianthan A: Physiology and pathophysiology of mucus and mucolytic use in critically ill patients. Crit Care. 29:682025. View Article : Google Scholar : PubMed/NCBI

Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J and Preissner KT: Neutrophil extracellular traps directly induce epithelial and endothelial cell death: A predominant role of histones. PLoS One. 7:e323662012. View Article : Google Scholar : PubMed/NCBI

Ulmer JS, Herzka A, Toy KJ, Baker DL, Dodge AH, Sinicropi D, Shak S and Lazarus RA: Engineering actin-resistant human DNase I for treatment of cystic fibrosis. Proc Natl Acad Sci USA. 93:8225–8229. 1996. View Article : Google Scholar : PubMed/NCBI

Lazzaretto B and Fadeel B: Intra- and extracellular degradation of neutrophil extracellular traps by macrophages and dendritic cells. J Immunol. 203:2276–2290. 2019. View Article : Google Scholar : PubMed/NCBI

Morita M, Stamp G, Robins P, Dulic A, Rosewell I, Hrivnak G, Daly G, Lindahl T and Barnes DE: Gene-targeted mice lacking the Trex1 (DNase III) 3′->5'DNA exonuclease develop inflammatory myocarditis. Mol Cell Biol. 24:6719–6727. 2004. View Article : Google Scholar : PubMed/NCBI

Iba T, Hashiguchi N, Nagaoka I, Tabe Y, Kadota K and Sato K: Heparins attenuated histone-mediated cytotoxicity in vitro and improved the survival in a rat model of histone-induced organ dysfunction. Intensive Care Med Exp. 3:362015. View Article : Google Scholar : PubMed/NCBI

Wildhagen KC, García de Frutos P, Reutelingsperger CP, Schrijver R, Aresté C, Ortega-Gómez A, Deckers NM, Hemker HC, Soehnlein O and Nicolaes GA: Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. Blood. 123:1098–1101. 2014. View Article : Google Scholar

Guzmán MA, Simpson L and Li RHL: Non-anticoagulant heparin attenuates histone-mediated platelet-leukocyte aggregation and neutrophil extracellular trap formation in a canine whole blood model. Front Vet Sci. 13:17784532026. View Article : Google Scholar : PubMed/NCBI

Osada K, Minami T, Arioka T, Sakai T, Tawara S, Kawasaki K, Fareed J and Matsuzaki O: Thrombomodulin alfa attenuates the procoagulant effect and cytotoxicity of extracellular histones through the promotion of protein C activation. Thromb Res. 160:51–57. 2017. View Article : Google Scholar : PubMed/NCBI

Abrams ST, Zhang N, Dart C, Wang SS, Thachil J, Guan Y, Wang G and Toh CH: Human CRP defends against the toxicity of circulating histones. J Immunol. 191:2495–2502. 2013. View Article : Google Scholar : PubMed/NCBI

Li Y, Zhao J, Wei J, Zhang Y, Zhang H, Li Y, Liao T, Hu Y, Yuan B, Zhang X, et al: Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: A multicenter retrospective cohort study. Respir Res. 26:282025. View Article : Google Scholar : PubMed/NCBI

Fukuta T, Okada H, Takemura G, Suzuki K, Takada C, Tomita H, Suzuki A, Oda K, Uchida A, Matsuo S, et al: Neutrophil elastase inhibition ameliorates Endotoxin-induced myocardial injury accompanying degradation of cardiac capillary glycocalyx. Shock. 54:386–393. 2020. View Article : Google Scholar :

Bidouard JP, Duval N, Kapui Z, Herbert JM, O'Connor SE and Janiak P: SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia-reperfusion injury. Eur J Pharmacol. 461:49–52. 2003. View Article : Google Scholar : PubMed/NCBI

Delbosc S, Rouer M, Alsac JM, Louedec L, Philippe M, Meilhac O, Whatling C and Michel JB: Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms. J Vasc Surg. 63:486–492. 2016. View Article : Google Scholar

Knight JS, Luo W, O'Dell AA, Yalavarthi S, Zhao W, Subramanian V, Guo C, Grenn RC, Thompson PR, Eitzman DT and Kaplan MJ: Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ Res. 114:947–956. 2014. View Article : Google Scholar : PubMed/NCBI

Zou P, Su XD, Tian W, Xie XY and Yang K: Peptidylarginine deiminase 4-mediated citrullination in human disease: Molecular mechanisms and therapeutic targeting. Front Pharmacol. 17:18540782026. View Article : Google Scholar : PubMed/NCBI

Du M, Yang W, Schmull S, Gu J and Xue S: Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction. Int Immunopharmacol. 78:1060552020. View Article : Google Scholar

Heger LA, Schommer N, Fukui S, Van Bruggen S, Sheehy CE, Chu L, Rajagopal S, Sivanandhan D, Ewenstein B and Wagner DD: Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis. Life Sci Alliance. 6:e2023020552023. View Article : Google Scholar : PubMed/NCBI

Li YW, Chen SX, Yang Y, Zhang ZH, Zhou WB, Huang YN, Huang ZQ, He JQ, Chen TF, Wang JF, et al: Colchicine inhibits NETs and alleviates cardiac remodeling after acute myocardial infarction. Cardiovasc Drugs Ther. 38:31–41. 2024. View Article : Google Scholar

Ding H, Cheng CK, Jiang M, Cheng X and Huang Y: Colchicine in cardiovascular medicine: Current perspectives on mechanisms and clinical therapeutics. Pharmacol Ther. 285:1090532026. View Article : Google Scholar : PubMed/NCBI

Shirakawa K, Kobayashi E, Ichihara G, Kitakata H, Katsumata Y, Sugai K, Hakamata Y and Sano M: H2 Inhibits the formation of neutrophil extracellular traps. JACC Basic Transl Sci. 7:146–161. 2022. View Article : Google Scholar : PubMed/NCBI

Khan MA, D'Ovidio A, Tran H and Palaniyar N: Anthracyclines suppress both NADPH Oxidase-dependent and -independent NETosis in human neutrophils. Cancers (Basel). 11:13282019. View Article : Google Scholar

Kindberg KM, Broch K, Andersen GØ, Anstensrud AK, Åkra S, Woxholt S, Tøllefsen IM, Ueland T, Amundsen BH, Kløw NE, et al: Neutrophil Extracellular traps in ST-Segment elevation myocardial infarction: Reduced by tocilizumab and associated with infarct size. JACC Adv. 3:1011932024. View Article : Google Scholar : PubMed/NCBI

Awasthi D, Nagarkoti S, Sadaf S, Chandra T, Kumar S and Dikshit M: Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis. Biochim Biophys Acta Mol Basis Dis. 1865:1655422019. View Article : Google Scholar : PubMed/NCBI

Burczyk G, Cichon I and Kolaczkowska E: Itaconate suppresses formation of neutrophil extracellular traps (NETs): Involvement of Hypoxia-Inducible factor 1α (Hif-1α) and heme oxygenase (HO-1). Front Immunol. 13:8646382022. View Article : Google Scholar