Document Detail

Matrix metalloproteinases synthesized in autosomal dominant polycystic kidney disease play a role in development of a concurrent abdominal aortic aneurysm.
MedLine Citation:
PMID:  15694696     Owner:  NLM     Status:  MEDLINE    
Abdominal aortic aneurysm is well known to be associated with autosomal dominant polycystic kidney disease. Kidney tubules of autosomal dominant polycystic kidney disease synthesize and secrete high levels of matrix metalloproteinase 2, 3, and 9, especially matrix metalloproteinase 2, and serum matrix metalloproteinase 1 and plasma matrix metalloproteinase 9 concentrations in the disease are significantly higher than those in healthy controls. On the other hand, matrix metalloproteinases play a crucial role in the pathogenesis of abdominal aortic aneurysm. Inflammatory cell expression of matrix metalloproteinase 9 plays a critical role in an experimental model of aortic aneurysm disease. Macrophage-derived matrix metalloproteinase 9 and mesenchymal cell matrix metalloproteinase 2 are both required and work in concert to produce abdominal aortic aneurysm. The plasma matrix metalloproteinase 9 levels are significantly higher in the patients with abdominal aortic aneurysm than in the patients with aortoiliac occlusive disease or the healthy patients. Remarkably elevated matrix metalloproteinase 2 mRNA and protein levels in abdominal aortic aneurysm tissues as compared with normal and atherosclerotic aortic tissues are detected, and matrix metalloproteinase 2 proteolytic activity is several-fold higher in abdominal aortic aneurysms than in other pathological or normal states. Patients with abdominal aortic aneurysm elevate matrix metalloproteinase 2 levels in the vasculature remote from the aorta, supporting both the systemic nature of aneurysmal disease and a primary role of matrix metalloproteinase 2 in aneurysm formation. The authors propose a novel hypothesis that matrix metalloproteinases, synthesized and secreted by kidney tubules of autosomal dominant polycystic kidney disease, play a critical role in development of a concurrent abdominal aortic aneurysm.
Hisato Takagi; Takuya Umemoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Medical hypotheses     Volume:  64     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2005  
Date Detail:
Created Date:  2005-02-07     Completed Date:  2005-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  778-81     Citation Subset:  IM    
Department of Cardiovascular Surgery, Sizuoka Medical Center, 762-1 Nagasawa, Shimizu-cho, Sunto-gun, Shizuoka 411-8611, Japan.
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MeSH Terms
Aortic Aneurysm, Abdominal / etiology*
Matrix Metalloproteinases / biosynthesis,  metabolism*
Polycystic Kidney, Autosomal Dominant / complications,  enzymology,  etiology*
Reg. No./Substance:
EC 3.4.24.-/Matrix Metalloproteinases

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