{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:45:56Z","timestamp":1784947556174,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Extracellular matrix degeneration, caused by matrix metalloproteinase\u20102, facilitates smooth muscle cell migration leading to medial layer decline and, ultimately, abdominal aortic aneurysm. It remains unclear what exactly causes aneurysms to rupture, which leads to death in most patients. The extracellular signal\u2010related kinase may be linked to the latter process. We aimed to clarify the role of extracellular signal\u2010related kinase in aortic aneurysm development and rupture in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Aortic fragments were harvested during open repair of nonruptured (<jats:italic>n<\/jats:italic>\u00a0=\u00a020) and ruptured (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) aneurysms. As control, nondilated aortas (<jats:italic>n<\/jats:italic>\u00a0=\u00a06) were obtained during autopsy. We determined levels of phosphorylated and total extracellular signal\u2010related kinase by Western blot, matrix metalloproteinase\u20102 by immunohistochemistry and medial layer thickness by conventional microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nonruptured aneurysms had 1\u00b78 times higher activation of extracellular signal\u2010related kinase (ratio: phosphorylated\/total) than controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7011). However, the ruptured aneurysms had only 0\u00b79 times the activation of controls (ns). Both nonruptured and ruptured aneurysms showed significantly higher matrix metalloproteinase\u20102 than controls (3\u00b78 and 4\u00b70\u2010times, respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7005). Of the medial layer thickness in controls, the median was 1\u00b75\u00a0mm, in nonruptured 1\u00b70\u00a0mm and in ruptured aneurysms 0\u00b77\u00a0mm. Activation of extracellular signal\u2010related kinase correlated positively to medial layer thickness (<jats:italic>R<\/jats:italic><jats:sub>s<\/jats:sub>\u00a0=\u00a00\u00b748; <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7014), but not to matrix metalloproteinase\u20102 (<jats:italic>R<\/jats:italic><jats:sub>s<\/jats:sub>\u00a0=\u00a0\u22120\u00b736; <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b710).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, nonruptured aneurysms are associated with increased extracellular signal\u2010related kinase activation while ruptured aneurysms are not. Extracellular signal\u2010related kinase was not related to total matrix metalloproteinase\u20102 expression. We therefore speculate that increased extracellular signal\u2010related kinase, in response to medial layer decline, could be protective against aneurysm rupture.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12618","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T11:53:35Z","timestamp":1458302015000},"page":"440-447","source":"Crossref","is-referenced-by-count":9,"title":["Activation of extracellular signal\u2010related kinase in abdominal aortic aneurysm"],"prefix":"10.1111","volume":"46","author":[{"given":"Menno E.","family":"Groeneveld","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"},{"name":"Department of Physiology ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max V.","family":"van Burink","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.V.","family":"Begieneman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cardiac Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"},{"name":"Netherlands Forensic Institute The Hague the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans W. M.","family":"Niessen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cardiac Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Wisselink","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed C.","family":"Eringa","sequence":"additional","affiliation":[{"name":"Department of Physiology ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kak K.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"},{"name":"Department of Physiology ICaR\u2010VU VU University Medical Center (VUmc) Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(98)70298-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2014.1905"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.3.1103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.6.713"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.01.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540600957438"},{"key":"e_1_2_10_8_1","first-page":"257","article-title":"Matrix metalloproteinases. 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