{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:44:12Z","timestamp":1790765052437,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,1,29]]},"abstract":"<jats:sec><jats:title>Background\u2014<\/jats:title><jats:p>Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage\/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results\u2014<\/jats:title><jats:p>We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1\/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1\/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circulationaha.112.123653","type":"journal-article","created":{"date-parts":[[2012,12,19]],"date-time":"2012-12-19T04:14:18Z","timestamp":1355890458000},"page":"463-475","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7"],"prefix":"10.1161","volume":"127","author":[{"given":"Andrea","family":"Vergani","sequence":"first","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tezza","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"D\u2019Addio","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Fotino","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Niewczas","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); Transplant Medicine, San Raffaele Hospital, Milan, Italy (A.V., F.D'A., R.B., A.P., E.A., P.F.); Diabetes Research Institute, University of Miami, Miami, FL (C.F., R.D.M., C.R., AP.); Pulmonary Medicine, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA (K.L.); Joslin..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bassi","sequence":"additional","affiliation":[{"name":"From the Transplantation Research Center (TRC), Nephrology Division, Boston Children\u2019s Hospital and Brigham and Women\u2019s Hospital\/Harvard Medical School, Boston, MA (A.V., S.T., F.D'A., R.B., S.K., R.A., M.H.S., P.F.); 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