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.
复制标题
DOI：
10.1016/j.atherosclerosis.2008.10.009
复制
发表时间：
2009-06-01
期刊：
影响因子：
5.3
通讯作者：
Jude, Brigitte
中科院分区：
文献类型：
--
作者：
Zawadzki, Christophe;Chatelain, Nicolas;Jude, Brigitte
背景：组织因子通路抑制剂-2 （TFPI-2）是一种在动脉粥样硬化斑块中表达的kunitz型丝氨酸蛋白酶抑制剂。TFPI-2基因的表观遗传调控，通过甲基化的CpG岛，已被提倡在癌症。我们假设TFPI-2基因甲基化可以调节动脉粥样硬化中TFPI-2的表达。方法：采用甲基化特异性PCR （MSP）和焦磷酸测序技术，鉴定59个颈动脉粥样硬化斑块和26个对照乳腺动脉中TFPI-2启动子的18个CpG。结果：MSP在16个斑块（27%）中显示TFPI-2基因（MSP+）甲基化，而在对照动脉中未发现MSP-甲基化。焦磷酸测序证实MSP+斑块的甲基化水平高于MSP-斑块和动脉（p=0.03和0.01）。此外，甲基化斑块中TFPI-2 mRNA水平低于未甲基化斑块和动脉（p=0.04和p=0.04）
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