{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:40:18Z","timestamp":1781332818575,"version":"3.54.1"},"reference-count":47,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"abstract":"<jats:p>Introduction: The aims of this study were to determine (1) whether endothelial nitric oxide synthase (eNOS) inhibition stimulates endothelial microvesicles (EMVs) release and (2) the effect of EMVs derived from eNOS-inhibited cells on endothelial cell eNOS, inflammation, apoptosis, and tissue-type plasminogen activator (t-PA). Methods: Human umbilical vein endothelial cells (HUVECs) were treated with the eNOS inhibitor (NG-nitro-&lt;sc&gt;l&lt;\/sc&gt;-arginine methyl ester [L-NAME], 300 \u00b5&lt;sc&gt;M&lt;\/sc&gt;) for 24 h. EMVs from untreated and L-NAME-treated cells were isolated, quantified, and exposed to HUVECs for 24 h. Results: eNOS-inhibited cells released significantly higher EMVs than untreated cells (81 \u00b1 13 vs. 41 \u00b1 15 EMV\/\u03bcL; p = 0.005). Expression of total eNOS (97.1 \u00b1 16.4 vs. 157.5 \u00b1 31.2 arbitrary units [AUs]; p = 0.01), p-eNOS (4.9 \u00b1 1.2 vs. 9.1 \u00b1 12.6 AUs; p = 0.02), and NO production (5.0 \u00b1 0.8 vs. 7.0 \u00b1 1.3 \u00b5mol\/L; p = 0.04) were significantly lower in cells treated with EMVs from L-NAME-treated cells. L-NAME-derived EMVs induced significantly higher IL-6 (38.3 \u00b1 10.3 vs. 21.0 \u00b1 3.8 pg\/mL; p = 0.01) and IL-8 (38.9 \u00b1 7.0 vs. 27.2 \u00b1 6.2 pg\/mL; p = 0.04) production concurrent with higher expression of p-NF-\u03baB p65 (Ser536) (9.7 \u00b1 1.6 vs. 6.1 \u00b1 1.2 AUs; p = 0.01). Expression of activated caspase-3 was higher (9.5 \u00b1 1.1 vs. 6.4 \u00b1 0.4 AUs) and t-PA lower (24.2 \u00b1 4.3 vs. 36.2 \u00b1 8.4 AUs; p = 0.04) in cells treated with L-NAME-derived EMVs. Conclusion: eNOS inhibition induces an increase in EMV release and an EMV phenotype with adverse cellular effects. <\/jats:p>","DOI":"10.1159\/000542280","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T17:12:16Z","timestamp":1733850736000},"page":"1-12","source":"Crossref","is-referenced-by-count":4,"title":["Microvesicles Derived from Nitric Oxide Synthase-Inhibited Endothelial Cells Promote Cell Dysfunction"],"prefix":"10.1159","author":[{"given":"Vinicius P.","family":"Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Stockelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u2019ayan V.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah 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