{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:42:06Z","timestamp":1791279726668,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n            Rupture of vulnerable plaques is the main cause of acute cardiovascular events. However, mechanisms responsible for transforming a stable into a vulnerable plaque remain elusive. Angiotensin II, a key regulator of blood pressure homeostasis, has a potential role in atherosclerosis. To study the contribution of angiotensin II in plaque vulnerability, we generated hypertensive hypercholesterolemic ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice with either normal or endogenously increased angiotensin II production (renovascular hypertension models). Hypertensive high angiotensin II ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice developed unstable plaques, whereas in hypertensive normal angiotensin II ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice plaques showed a stable phenotype. Vulnerable plaques from high angiotensin II ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice had thinner fibrous cap (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01), larger lipid core (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01), and increased macrophage content (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01) than even more hypertensive but normal angiotensin II ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. Moreover, in mice with high angiotensin II, a skewed T helper type 1-like phenotype was observed. Splenocytes from high angiotensin II ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice produced significantly higher amounts of interferon (IFN)-\u03b3 than those from ApoE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice with normal angiotensin II; secretion of IL4 and IL10 was not different. In addition, we provide evidence for a direct stimulating effect of angiotensin II on lymphocyte IFN-\u03b3 production. These findings suggest a new mechanism in plaque vulnerability demonstrating that angiotensin II, within the context of hypertension and hypercholesterolemia, independently from its hemodynamic effect behaves as a local modulator promoting the induction of vulnerable plaques probably via a T helper switch.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000140269.55873.7b","type":"journal-article","created":{"date-parts":[[2004,8,10]],"date-time":"2004-08-10T00:16:27Z","timestamp":1092096987000},"page":"277-282","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":116,"title":["Endogenous Angiotensin II Induces Atherosclerotic Plaque Vulnerability and Elicits a Th1 Response in ApoE\n            <sup>\u2212\/\u2212<\/sup>\n            Mice"],"prefix":"10.1161","volume":"44","author":[{"given":"Lucia","family":"Mazzolai","sequence":"first","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel A.","family":"Duchosal","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Korber","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Bouzourene","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Franc\u0327ois","family":"Aubert","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hao","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Vallet","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans- R.","family":"Brunner","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u0308rg","family":"Nussberger","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Gabbiani","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hayoz","sequence":"additional","affiliation":[{"name":"From the Service of Angiology (L.M., M.K., K.B., J.F.A., H.R.B., J.N., D.H.) and the Service of Hematology (M.A.D, V.V.), CHUV, University of Lausanne, Switzerland; Department of Pathology (H.H., G.G.), University of Geneva, Switzerland. H.H. is currently affiliated with the Department of Pathology, National Cardiovascular Center, Osaka, Fujishirodai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000087480.94275.97"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.21.9.1464"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.31.6.1331"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1656136"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.35.4.985"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.15.3.327"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.101.13.1586"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200001203420301"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92889-N"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7818"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.3.448"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.29.4.1025"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198701000-00007"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2787"},{"key":"e_1_3_3_15_2","unstructured":"Nussberger J. 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