{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:08:55Z","timestamp":1792447735331,"version":"4.5.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2018,8,31]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Giant cell arteritis (GCA)\u2014a primary vasculitis of medium and large arteries\u2014is associated with vessel wall damage, elastic membrane fragmentation, and vascular remodeling. Proteinases are believed to contribute to pathogenesis by degrading extracellular matrix and causing tissue injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The MMP (matrix metalloproteinase)-9\u2014a type IV collagenase\u2014is produced in the vasculitic lesions of GCA. It is unknown which pathogenic processes are MMP-9 dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      The tissue transcriptome of GCA-affected temporal arteries contained high amounts of MMP-9 transcripts, and immunostaining for pro-MMP-9 localized the enzyme to wall-infiltrating macrophages. MMP-2 and MMP-9 transcripts were also abundant in monocytes and monocyte-derived macrophages from patients with GCA. Patient-derived monocytes outperformed healthy monocytes in passing through engineered basement membranes. GCA CD (cluster of differentiation) 4\n                      <jats:sup>+<\/jats:sup>\n                      T cells required MMP-9\u2013producing monocytes to penetrate through matrix built from type IV collagen. In vivo functions of MMP-9 were tested in a human artery-SCID (severe combined immunodeficiency) chimera model by blocking enzyme activity with a highly specific monoclonal antibody or by injecting rMMP-9 (recombinant MMP-9). Inhibiting MMP-9 activity profoundly suppressed vascular injury, decreased the density of inflammatory infiltrates (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), reduced intramural neoangiogenesis (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), and prevented intimal layer hyperplasia (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). rMMP-9 amplified all domains of vasculitic activity, promoted assembly of T-cell infiltrates (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05), intensified formation of new microvessels (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), and worsened intimal thickening (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Systemic delivery of N-acetyl-proline-glycine-proline\u2014a matrikine produced by MMP-9\u2013mediated gelatinolysis\u2014had limited vasculitogenic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>In large vessel vasculitis, MMP-9 controls the access of monocytes and T cells to the vascular wall. T cells depend on MMP-9\u2013producing monocytes to pass through collagen IV-containing basement membrane. Invasion of vasculitogenic T cells and monocytes, formation of neoangiogenic networks, and neointimal growth all require the enzymatic activity of MMP-9, identifying this protease as a potential therapeutic target to restore the immunoprivilege of the arterial wall in large vessel vasculitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.118.313206","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T05:15:37Z","timestamp":1530594937000},"page":"700-715","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":160,"title":["MMP (Matrix Metalloprotease)-9\u2013Producing Monocytes Enable T Cells to Invade the Vessel Wall and Cause Vasculitis"],"prefix":"10.1161","volume":"123","author":[{"given":"Ryu","family":"Watanabe","sequence":"first","affiliation":[{"name":"From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Maeda","sequence":"additional","affiliation":[{"name":"From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Pathology (G.J.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Zeisbrich","sequence":"additional","affiliation":[{"name":"From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brockett","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc, Foster City, CA (R.B., A.E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc, Foster City, CA (R.B., A.E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Stanford University School of Medicine, CA (L.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"From the Division of Immunology and Rheumatology, Department of Medicine (R.W., T.M., H.Z., M.Z., J.J.G., C.M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia 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