{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:04:45Z","timestamp":1784930685100,"version":"3.55.0"},"posted":{"date-parts":[[2026,3,13]]},"group-title":"Physiology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>AIM<\/jats:title>\n                  <jats:p>Chemokine signaling contributes to vascular inflammation and dysfunction in hypertension, yet the intracellular mechanisms linking CCL5\/CCR5 activation to vascular impairment remain unclear. We tested the hypothesis that angiotensin II (Ang II) amplifies CCL5\/CCR5 signaling to promote mitochondrial dysfunction and oxidative stress in the vasculature.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Wild-type and CCR5-deficient mice were infused with Ang II for 14 days, and separate cohorts received recombinant CCL5. Vascular function and remodeling were assessed in aorta and mesenteric arteries, while mitochondrial respiration, membrane potential, and reactive oxygen species (ROS) production were evaluated in vascular smooth muscle cells (VSMCs).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Ang II increased circulating CCL5 levels and upregulated vascular CCR5 expression. CCR5 deficiency protected against Ang II\u2013induced vascular dysfunction, remodeling, and inflammation. CCL5 infusion impaired endothelium-dependent relaxation and enhanced contractility without inducing structural remodeling. In VSMCs, CCL5 disrupted mitochondrial respiration, reduced maximal respiratory capacity, altered membrane potential, and increased mitochondrial ROS in a CCR5-dependent manner. Mitochondrial antioxidant treatment restored endothelial function but did not normalize enhanced contractility. In addition, vessels from CCL5-treated mice were unresponsive to acute mitochondrial uncoupling, consistent with impaired mitochondrial bioenergetic reserve.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSION<\/jats:title>\n                  <jats:p>Ang II amplifies CCL5\/CCR5 signaling to drive mitochondrial dysfunction and oxidative stress, thereby promoting vascular impairment, and identify this pathway as a potential therapeutic target in hypertension.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.10.710946","type":"posted-content","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:40:14Z","timestamp":1773441614000},"source":"Crossref","is-referenced-by-count":0,"title":["CCR5\/CCL5-Dependent Mitochondrial Dysfunction Contributes to Angiotensin II\u2013 Induced Vascular Impairment in Mice"],"prefix":"10.64898","author":[{"given":"Gustavo Felix","family":"Pimenta","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United State of America"},{"name":"Department of Pharmacology, University of Sao Paulo, Ribeirao Preto, SP, Brazil"},{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7067-4048","authenticated-orcid":false,"given":"Ariane","family":"Bruder","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United State of America"},{"name":"Center for Lung Biology, University of South Alabama, Mobile, AL, United State of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Beling","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United State of America"},{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United State of America"},{"name":"Center for Lung Biology, University of South Alabama, Mobile, AL, United State of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Oliveira de Moraes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, 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