{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:20:22Z","timestamp":1773451222196,"version":"3.50.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:p>\n            In deoxycorticosterone acetate (DOCA)-salt hypertension, the endothelin-1 system is activated and plays a role in cardiac fibrosis. Remodeling of extracellular matrix (ECM) may lead to interstitial fibrosis, which may contribute to heart failure. Imbalance in synthesis and degradation of the ECM by matrix metalloproteinases (MMPs) as well as inflammation may play a role in matrix protein deposition and cardiac remodeling in hypertension. We measured expression of the extracellular matrix protein fibronectin, the activity of the gelatinases MMP-2 and MMP-9, the proinflammatory transcription factor NF\u03baB, and the adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and platelet-endothelial cell adhesion molecule (PECAM)-1 in hearts of DOCA-salt hypertensive (DS) rats treated or not with the endothelin ET\n            <jats:sub>A<\/jats:sub>\n            antagonist BMS 182874 (BMS). Unilaterally nephrectomized rats (UniNx) were compared with DS rats treated or not with BMS 40 mg\/kg\/d. Fibronectin deposition was detectable at the first week, and remained elevated thereafter. This increase was abrogated by administration of the ET\n            <jats:sub>A<\/jats:sub>\n            antagonist. Enzymatic activity of gelatinases was increased (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01) in DS compared with control during the first and second week. BMS blocked the increase of MMP-2 and MMP-9 activity at week 1 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05); MMP activity remained lower than in DS at week 2. NF-\u03baB binding activity in DS was higher (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) than it was in controls during the second week, and was reduced by BMS. The adhesion molecules VCAM-1 and PECAM-1, and the antiapoptotic molecule xIAP were upregulated in the left ventricle of the heart of DS rats and downregulated in the rats treated with the ET\n            <jats:sub>A<\/jats:sub>\n            antagonist. In conclusion, cardiac extracellular remodeling in rats with endothelin-dependent hypertension was associated with increased fibronectin, MMP activity, and upregulation of inflammatory mediators, all of which were reduced by ET\n            <jats:sub>A<\/jats:sub>\n            antagonism.\n          <\/jats:p>","DOI":"10.1161\/hy0202.103481","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"679-684","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Fibrosis, Matrix Metalloproteinases, and Inflammation in the Heart of DOCA-Salt Hypertensive Rats: Role of ET\n            <sub>A<\/sub>\n            Receptors"],"prefix":"10.1161","volume":"39","author":[{"given":"Fatima Z.","family":"Ammarguellat","sequence":"first","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe O.","family":"Gannon","sequence":"additional","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhad","family":"Amiri","sequence":"additional","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto L.","family":"Schiffrin","sequence":"additional","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.3.294"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.24.2.183"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.2.319"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.6.1444"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Park JB Schiffrin EL. Cardiac and vascular fibrosis and hypertrophy in aldosterone-infused rats: role of endothelin-1. Am J Hypertens. 2001; in press.","DOI":"10.1016\/S0895-7061(01)02291-9"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00029-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00104-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.8.1850705"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.815400"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000052610"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(00)00200-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.75.3.7520371"},{"key":"e_1_3_2_13_2","first-page":"86","volume":"74","year":"1996","unstructured":"Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 1996; 74: 86\u2013107.","journal-title":"Lab Invest"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610173351603"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.75.6.7955143"},{"key":"e_1_3_2_16_2","first-page":"322","volume":"23","year":"2000","unstructured":"Kirshenbaum LA. Bcl-2 intersects the NFkappaB signalling pathway and suppresses apoptosis in ventricular myocytes. Clin Invest Med. 2000; 23: 322\u2013330.","journal-title":"Clin Invest Med"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.88.3.282"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.211"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199715120-00011"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600620215"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.35.1.193"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.32.4.770"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.34.4.907"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.3.H984"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704103361506"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90506-5"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.7.806"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-000-0066-3"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.2.781"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.5.1345"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3272"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.13053"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1997.sp004025"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780164"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1997.0062"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/376167a0"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203238"},{"key":"e_1_3_2_39_2","first-page":"26452","volume":"276","year":"2001","unstructured":"Birkey RS, Wurthner JU, Parks WT, Roberts AB, Duckett CS. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-\u03b2 signaling. J Biol Chem. 2001; 276: 26452\u201326459.","journal-title":"J Biol Chem"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.1.179"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117269"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hy0202.103481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T02:35:28Z","timestamp":1715654128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hy0202.103481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,2]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,2]]}},"alternative-id":["10.1161\/hy0202.103481"],"URL":"https:\/\/doi.org\/10.1161\/hy0202.103481","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,2]]},"assertion":[{"value":"2001-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-11-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}