{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:26:54Z","timestamp":1792614414653,"version":"4.5.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Coronary artery thrombosis can occur in the absence of plaque rupture because of superficial erosion. Erosion-prone atheromata associate with more neutrophil extracellular traps (NETs) than lesions with stable or rupture-prone characteristics. The effects of NETs on endothelial cell (EC) inflammatory and thrombogenic properties remain unknown. We hypothesized that NETs alter EC functions related to erosion-associated thrombosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Exposure of human ECs to NETs increased VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA and protein expression in a time- and concentration-dependent manner. THP-1 monocytoid cells and primary human monocytes bound more avidly to NET-treated human umbilical vein ECs than to unstimulated cells under flow. Treatment of human ECs with NETs augmented the expression of TF (tissue factor) mRNA, increased EC TF activity, and hastened clotting of recalcified plasma. Anti-TF-neutralizing antibody blocked NET-induced acceleration of clotting by ECs. NETs alone did not exhibit TF activity or acceleration of clotting in cell-free assays. Pretreatment of NETs with anti-interleukin (IL)-1\u03b1\u2013neutralizing antibody or IL-1Ra (IL-1 receptor antagonist)\u2014but not with anti-IL-1\u03b2\u2013neutralizing antibody or control IgG\u2014blocked NET-induced VCAM-1, ICAM-1, and TF expression. Inhibition of cathepsin G, a serine protease abundant in NETs, also limited the effect of NETs on EC activation. Cathepsin G potentiated the effect of IL-1\u03b1 on ECs by cleaving the pro-IL-1\u03b1 precursor and releasing the more potent mature IL-1\u03b1 form.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>NETs promote EC activation and increased thrombogenicity through concerted action of IL-1\u03b1 and cathepsin G. Thus, NETs may amplify and propagate EC dysfunction related to thrombosis because of superficial erosion.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311150","type":"journal-article","created":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T09:10:09Z","timestamp":1530781809000},"page":"1901-1912","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":344,"title":["Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1\u03b1 and Cathepsin G"],"prefix":"10.1161","volume":"38","author":[{"given":"Eduardo J.","family":"Folco","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine (E.J.F., T.L.M., A.V., G.F., B.B.-S., O.P., M.N., P.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Mawson","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine 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