{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:07:58Z","timestamp":1760954878386},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1_supplement","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,7,4]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Autoimmunity may exacerbate vascular disease, particularly in the form of anti-endothelial cell (EC) antibodies. The increased morbidity of cardiovascular diseases in concert with diabetes mellitus, hypertension, and other systemic illnesses may reflect the increase presence and potency of these antibodies. Matrix-embedded ECs act as powerful regulators of vascular repair accompanied by significant reduction in expected systemic and local inflammation. We compared the immune response against free and matrix-embedded ECs in nai\u0308ve mice and mice with heightened EC immune reactivity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Mice were presensitized to EC with repeated (days 0, 21, 35) subcutaneous injections of saline-suspended porcine EC (PAE) (5\u00d710\n            <jats:sup>5<\/jats:sup>\n            cells). Controls received saline injections. On day 42, mice received 5\u00d710\n            <jats:sup>5<\/jats:sup>\n            matrix-embedded or free PAEs. Circulating PAE-specific antibodies and effector T-cells were analyzed via flow cytometry, and xenoreactive lymphocytes via ELISPOT, 90 days after implantation. PAE-specific antibody-titers, frequency of CD4\n            <jats:sup>+<\/jats:sup>\n            -effector cells, and xenoreactive splenocytes were 2- to 4-fold lower (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001) when nai\u0308ve mice were injected with matrix-embedded instead of saline-suspended PAEs. Though basal levels of circulating antibodies were significantly elevated after serial PAE injections (2210\u00b1341 mean fluorescence intensity, day 42) and almost doubled again 90 days after injection of a fourth set of free PAEs, antibody levels declined by half in recipients of matrix-embedded PAEs at day 42 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001). Levels of CD4\n            <jats:sup>+<\/jats:sup>\n            -effector cells and xenoreactive splenocytes showed similar results.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Implantation of free PAE elicits a significant immune response in nai\u0308ve mice and even more pronounced in mice with predeveloped anti-endothelial immunity. Matrix-embedding protects xenogeneic ECs against immune reaction in nai\u0308ve mice and to a similar extent in mice with heightened immune reactivity. Matrix-embedded EC might offer a promising approach for treatment of advanced cardiovascular disease.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.000687","type":"journal-article","created":{"date-parts":[[2006,7,7]],"date-time":"2006-07-07T01:56:58Z","timestamp":1152237418000},"update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Cell\u2013Matrix Contact Prevents Recognition and Damage of Endothelial Cells in States of Heightened Immunity"],"prefix":"10.1161","volume":"114","author":[{"given":"Heiko","family":"Methe","sequence":"first","affiliation":[{"name":"From Harvard-MIT Division of Health Sciences and Technology (H.M., E.R.E.), Massachusetts Institute of Technology, Cambridge, Mass; Cardiovascular Division (E.R.E.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elazer R.","family":"Edelman","sequence":"additional","affiliation":[{"name":"From Harvard-MIT Division of Health Sciences and Technology (H.M., E.R.E.), Massachusetts Institute of Technology, Cambridge, Mass; Cardiovascular Division (E.R.E.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","first-page":"426","volume":"133","year":"1988","unstructured":"Pober JS. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol. 1988; 133: 426\u2013433.","journal-title":"Am J Pathol"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(88)90196-7"},{"key":"e_1_3_3_3_2","first-page":"410","volume":"88","year":"1992","unstructured":"Wangel AG, Kontiainen S, Scheinin T, Schlenzka A, Wangel D, Maenpaa J. Anti-EC antibodies in insulin-dependent diabetes mellitus. 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