Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MMP3, MMP9, and PAI-1 are present at increased levels in abdominal aortic aneurysms (AAAs). The promoters of these genes contain polymorphisms, with alleles that exhibit different transcriptional activities in vitro. Association studies were performed using these polymorphisms and DNA isolated from 47 AAA patients, 57 intracranial aneurysm (IA) patients, and 174 controls, all from Finland. PAI-1 and MMP9 genotypes did not associate with aneurysms. The frequency of the 5A MMP3 allele was somewhat higher in the AAA than that in the control group (P = 0.0609 after Bonferroni correction), whereas the MMP3 allele frequencies in the IA group did not differ from those of the controls (P = 0.9667). These findings suggest that the transcriptionally more active 5A MMP3 allele might be a genetic risk factor for AAA among Finns. They are in agreement with previous studies demonstrating higher level of MMP3 expression in AAA than in control tissues.
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PMID:Genetic analysis of MMP3, MMP9, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms. 1055 9

Data have been accumulating that indicate that matrix metalloproteinase (MMP) gene polymorphisms contribute to inter-individual differences in susceptibility to and outcome of cardiovascular disease. This is currently best exemplified by the MMP3 gene 5A/6A polymorphism which has an effect on MMP3 expression and has been shown to be associated with coronary stenosis, myocardial infarction, coronary artery calcification, post-angioplasty coronary restenosis, carotid atherosclerosis, stroke, arterial stiffness, and blood pressure. Functional polymorphisms in the MMP1, MMP2, MMP7, MMP9, MMP12, and MMP13 genes have also been related to coronary artery disease, arterial stiffness, and/or abdominal aortic aneurysm. These genetic findings support the notion that MMPs play important roles in the pathogenesis of these conditions. There is also some evidence suggesting that MMP genotyping could aid in identifying patients who are likely to have unfavourable prognosis and/or adverse response to treatment.
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PMID:Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. 1612 19

Statins may reduce abdominal aortic aneurysm (AAA) progression. We sought to measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase (MMP) expression and/or activity in human AAA. Tissue from human AAAs at surgical repair was obtained from patients who were either not on statins (NST, n = 19) or treated with AT (n = 19). Immunoblots measured expression and zymography measured activity. Expression of most proteins was greater in the central compared with distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against Decapentaplegia (SMAD2) expression did not differ with treatment. There was a trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in the AT-treatment group. In contrast, AT-treated samples had significantly reduced MMP13 (P = .02), latent-transforming growth factor (TGF)-beta (P = .02), and phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that the AT-mediated decrease in MMP expression and activity reduces TGF-beta signaling in the central region of human AAAs.
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PMID:Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms. 2003 37