title: Activation of extracellular signal-related kinase in abdominal aortic aneurysm.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Vascular Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.|Department of Physiology, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Menno E
authors.initials: ME
authors.lastname: Groeneveld
authors.affiliation: Department of Vascular Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Max V
authors.initials: MV
authors.lastname: van Burink
authors.affiliation: Department of Pathology and Cardiac Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.|Netherlands Forensic Institute, The Hague, the Netherlands.
authors.forename: Mark P V
authors.initials: MP
authors.lastname: Begieneman
authors.affiliation: Department of Pathology and Cardiac Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Vascular Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Wisselink
authors.affiliation: Department of Physiology, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Ed C
authors.initials: EC
authors.lastname: Eringa
authors.affiliation: Department of Vascular Surgery, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.|Department of Physiology, ICaR-VU, VU University Medical Center (VUmc), Amsterdam, the Netherlands.
authors.forename: Kak K
authors.initials: KK
authors.lastname: Yeung
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D001019:Aortic Rupture / Q000378:metabolism*; D001344:Autopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Abdominal aortic aneurysm; ERK1/2; extracellular matrix; matrix metalloproteinases