{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T12:30:04Z","timestamp":1793017804536,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Although combination antiretroviral therapy has increased life expectancy in people living with HIV, it has led to a marked increase in the prevalence of hypertension, the cause of which is unknown. Despite combination antiretroviral therapy, HIV-derived proteins remain expressed and produced by CD4\n              <jats:sup>+<\/jats:sup>\n              T lymphocytes in people living with HIV. However, their contribution to HIV-associated hypertension and impaired endothelium-dependent relaxation remains ill defined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Here, we tested the hypothesis that CD4\n              <jats:sup>+<\/jats:sup>\n              T cells expressing viral proteins contribute to endothelial dysfunction and hypertension using the Tg26 mouse model of HIV that expresses 7 of the 9 HIV proteins under the long terminal repeat promoter. We used male and female mice, bone marrow transplantation (BMT), adoptive transfer of CD4\n              <jats:sup>+<\/jats:sup>\n              T cells, and aorta specimen discarded from people living with HIV.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              We reported that intact Tg26 mice and mice receiving BMT (Tg26\u2192WT) or CD4\n              <jats:sup>+<\/jats:sup>\n              T cells from Tg26 mice display impaired endothelium-dependent relaxation and hypertension. Conversely, BMT from WT mice into Tg26 mice, inhibition of T cell activation, and CD4\n              <jats:sup>+<\/jats:sup>\n              T cell depletion restored endothelial function and blood pressure in Tg26 mice. Cytokine profiling revealed that Tg26 mice, Tg26\u2192WT, and Tg26 CD4\n              <jats:sup>+<\/jats:sup>\n              T cells consistently exhibit high interleukin 1\u03b1 (IL-1\u03b1) levels with no significant increase in other cytokines, whereas BMT from WT mice into Tg26 mice reduced IL-1\u03b1 levels. IL-1\u03b1 neutralization reduced blood pressure and restored endothelial function in Tg26 mice. To investigate the role of CD4\n              <jats:sup>+<\/jats:sup>\n              T cells and IL-1\u03b1 in endothelial dysfunction, we developed an aorta-immune cell coculture system. Exposure of WT aortas to Tg26 CD4\n              <jats:sup>+<\/jats:sup>\n              T cells impaired endothelium-dependent relaxation, which was blocked by IL-1\u03b1\u2013neutralizing antibody. While investigating the mechanisms of endothelial dysfunction, we reported that Tg26 mice, Tg26\u2192WT aorta exhibit high NADPH oxidase (NOX) 1 expression. IL-1\u03b1 exposure increased NOX1 in human microvascular endothelial cells, and NOX1 blockade restored endothelial function in Tg26 and Tg26\u2192WT arteries, whereas NOX1 deficiency protected against Tg26 BMT-induced impaired endothelium-dependent relaxation and hypertension. Aortas from people living with HIV exhibit high NOX1 levels, and exposure of human aorta to Tg26 T cells increased NOX1 expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              We provide the first evidence that CD4\n              <jats:sup>+<\/jats:sup>\n              T cells expressing HIV viral proteins induced hypertension through IL-1\u03b1\u2013mediated increases in vascular NOX1, which impairs endothelial function in males and females.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.124.070538","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:00:23Z","timestamp":1738749623000},"page":"1187-1203","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["CD4\n            <sup>+<\/sup>\n            T Cells Expressing Viral Proteins Induce HIV-Associated Endothelial Dysfunction and Hypertension Through Interleukin 1\u03b1\u2013Mediated Increases in Endothelial NADPH Oxidase 1"],"prefix":"10.1161","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-3788","authenticated-orcid":true,"given":"Taylor C.","family":"Kress","sequence":"first","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-6487","authenticated-orcid":true,"given":"Candee T.","family":"Barris","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9886-6755","authenticated-orcid":true,"given":"Laszlo","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0792-6498","authenticated-orcid":true,"given":"Beryl N.","family":"Khakina","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5438-0030","authenticated-orcid":true,"given":"Coleton R.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-318X","authenticated-orcid":true,"given":"Thiago","family":"Bruder-Nascimento","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"},{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile (T.B.-N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0184-8321","authenticated-orcid":true,"given":"David W.","family":"Stepp","sequence":"additional","affiliation":[{"name":"Vascular Biology Center (T.C.K., C.T.B., L.K., B.N.K., C.R.J., T.B.-N., D.W.S., S.K., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger","family":"MacArthur","sequence":"additional","affiliation":[{"name":"Department of Medicine (R.M., V.S.P., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8402-2682","authenticated-orcid":true,"given":"Vijay S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine (R.M., V.S.P., E.J.B.d.C.), University of South Alabama, Mobile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-5276","authenticated-orcid":true,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics (J.C.), University of South Alabama, 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