Activation of extracellular signal-related kinase in abdominal aortic aneurysm

Background Extracellular matrix degeneration, caused by matrix metalloproteinase‐2, 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....

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Veröffentlicht in:European journal of clinical investigation Jg. 46; H. 5; S. 440 - 447
Hauptverfasser: Groeneveld, Menno E., van Burink, Max V., Begieneman, Mark P.V., Niessen, Hans W. M., Wisselink, Willem, Eringa, Ed C., Yeung, Kak K.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Blackwell Publishing Ltd 01.05.2016
Schlagworte:
Abdominal aortic aneurysm
Aged
Aortic Aneurysm, Abdominal - metabolism
Aortic Rupture - metabolism
Autopsy
Blotting, Western
Case-Control Studies
ERK1/2
extracellular matrix
Female
Humans
Male
Matrix Metalloproteinase 2 - metabolism
matrix metalloproteinases
Middle Aged
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
ERK1/2
matrix metalloproteinases
extracellular matrix
Abdominal aortic aneurysm
ISSN:0014-2972, 1365-2362
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Zusammenfassung:Background Extracellular matrix degeneration, caused by matrix metalloproteinase‐2, 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‐related kinase may be linked to the latter process. We aimed to clarify the role of extracellular signal‐related kinase in aortic aneurysm development and rupture in patients. Design Aortic fragments were harvested during open repair of nonruptured (n = 20) and ruptured (n = 8) aneurysms. As control, nondilated aortas (n = 6) were obtained during autopsy. We determined levels of phosphorylated and total extracellular signal‐related kinase by Western blot, matrix metalloproteinase‐2 by immunohistochemistry and medial layer thickness by conventional microscopy. Results Nonruptured aneurysms had 1·8 times higher activation of extracellular signal‐related kinase (ratio: phosphorylated/total) than controls (P = 0·011). However, the ruptured aneurysms had only 0·9 times the activation of controls (ns). Both nonruptured and ruptured aneurysms showed significantly higher matrix metalloproteinase‐2 than controls (3·8 and 4·0‐times, respectively; P < 0·005). Of the medial layer thickness in controls, the median was 1·5 mm, in nonruptured 1·0 mm and in ruptured aneurysms 0·7 mm. Activation of extracellular signal‐related kinase correlated positively to medial layer thickness (Rs = 0·48; P = 0·014), but not to matrix metalloproteinase‐2 (Rs = −0·36; P = 0·10). Conclusions In this study, nonruptured aneurysms are associated with increased extracellular signal‐related kinase activation while ruptured aneurysms are not. Extracellular signal‐related kinase was not related to total matrix metalloproteinase‐2 expression. We therefore speculate that increased extracellular signal‐related kinase, in response to medial layer decline, could be protective against aneurysm rupture.
Bibliographie:ArticleID:ECI12618
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SourceType-Scholarly Journals-1
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content type line 23
ISSN:0014-2972
1365-2362
DOI:10.1111/eci.12618