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Given that CHIKV stimulates reactive oxygen species (ROS) and pro- and anti-inflammatory cytokines, events that disrupt vascular homeostasis, we hypothesized that CHIKV induces arterial dysfunction by directly impacting redox-related mechanisms in vascular cells. Wild-type (WT) and iNOS knockout (iNOS\u2212\/\u2212) mice were administered either CHIKV (1.0 \u00d7 106 PFU\/\u00b5L) or Mock vehicle via the intracaudal route. In vivo, CHIKV infection induced vascular dysfunction (assessed by a wire myograph), decreased systolic blood pressure (tail-cuff plethysmography), increased IL-6 and IFN-\u03b3, but not TNF-\u03b1 levels (determined by ELISA), and increased protein content by Western blot. Marked contractile hyporesponsiveness to phenylephrine was observed 48 h post-infection, which was restored by endothelium removal. L-NAME, 1400W, Tiron, and iNOS gene deletion prevented phenylephrine hyporesponsiveness. CHIKV infection increased vascular nitrite concentration (Griess reaction) and superoxide anion (O2\u2022\u2212) generation (lucigenin chemiluminescence), and decreased hydrogen peroxide (H2O2, by Amplex Red) levels 48 h post-infection, alongside increased TBARS levels. In vitro, CHIKV infected endothelial cells (EA.hy926) and upregulated ICAM-1 and iNOS protein expression (determined by Western blot). These data support the conclusion that CHIKV-induced alterations in vascular ROS\/NF-kB\/iNOS\/NO signaling potentially contribute to cardiovascular events associated with Chikungunya infection.<\/jats:p>","DOI":"10.3390\/cells13211770","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T05:07:22Z","timestamp":1730092042000},"page":"1770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Acute Chikungunya Infection Induces Vascular Dysfunction by Directly Disrupting Redox Signaling in Endothelial Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-0193","authenticated-orcid":false,"given":"Jos\u00e9 Teles de","family":"Oliveira-Neto","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano de P.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-1576","authenticated-orcid":false,"given":"Daniel","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirele R.","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano V.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"},{"name":"Academic Unit of Health Sciences, Federal University of Jatai, Jata\u00ed 75804-068, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5428-8490","authenticated-orcid":false,"given":"Paula R.","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"},{"name":"Institute of Biomedical Sciences, University of Sao Paulo, Ribeir\u00e3o Preto 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-8972","authenticated-orcid":false,"given":"Alecsander F.","family":"Bressan","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Faculty of Medicine, Federal University of Mato Grosso, Cuiab\u00e1 79070-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-7946","authenticated-orcid":false,"given":"Josiane F.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-4290","authenticated-orcid":false,"given":"Tiago J.","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of Sao Paulo, Ribeir\u00e3o Preto 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5174-5710","authenticated-orcid":false,"given":"Rafael M.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"},{"name":"Academic Unit of Health Sciences, Federal University of Jatai, Jata\u00ed 75804-068, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5253-4918","authenticated-orcid":false,"given":"Daniella","family":"Bonaventura","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eurico de","family":"Arruda-Neto","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-0707","authenticated-orcid":false,"given":"Rita C.","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana P.","family":"Abr\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"},{"name":"Master\u2019s Education Institute President Antonio Carlos (IMEPAC), Araguari 38025-440, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, June 02). 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