Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques.
Atherosclerosis
; 204(2): e4-14, 2009 Jun.
Article
in En
| MEDLINE
| ID: mdl-19081094
BACKGROUND: The tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine-protease inhibitor which is expressed in atherosclerotic plaques. Epigenetic regulation of the TFPI-2 gene, through methylation of CpG islands, has been advocated in cancer. We hypothesized that TFPI-2 gene methylation could regulate TFPI-2 expression in atherosclerosis. METHODS: We used Methylation Specific PCR (MSP) and pyrosequencing in order to identify 18 CpG of the TFPI-2 promoter, in 59 carotid atherosclerotic plaques and 26 control mammary arteries. RESULTS: MSP showed methylation of the TFPI-2 gene (MSP+) in 16 plaques (27%), while no methylation (MSP-) was found in control arteries. Pyrosequencing confirmed that MSP+ plaques presented higher methylation levels than MSP- ones and arteries (p=0.03 and 0.01). Moreover, the TFPI-2 mRNA levels were lower in methylated plaques than in unmethylated ones and than in arteries (p=0.04 and <0.0001). The methylated plaques contained less lipids and macrophage infiltration than unmethylated ones. Their TFPI-2 immunoreactivity was mainly detected in the macrophages located in the media on the adventitial side, rather than in the lipid-rich core. CONCLUSION: Methylation of the TFPI-2 gene takes place in atherosclerotic plaques and is associated with decreased TFPI-2 expression. The place of this process in atherosclerosis progression remains to be investigated.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycoproteins
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Carotid Arteries
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Carotid Artery Diseases
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Promoter Regions, Genetic
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CpG Islands
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DNA Methylation
Type of study:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Atherosclerosis
Year:
2009
Document type:
Article
Affiliation country:
Country of publication: