کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2893516 | 1172415 | 2009 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Tissue Factor Pathway Inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques Tissue Factor Pathway Inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques](/preview/png/2893516.png)
SummaryBackgroundThe 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.MethodsWe 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.ResultsMSP 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.ConclusionMethylation 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.
Journal: Atherosclerosis - Volume 204, Issue 2, June 2009, Pages e4–e14