title: Plasma homocysteine involved in methylation and expression of thrombomodulin in cerebral infarction.
abstract: Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X(2) = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = -0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury.
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, PR China; Department of Neurology, The First Affiliated Hospital of Baotou Medical College, Baotou, 014010, PR China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pathology, Baotou Medical College, Baotou, 014060, PR China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Baotou Medical College, Baotou, 014060, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Baotou Medical College, Baotou, 014060, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, PR China. Electronic address: zhoushengnian163@163.com.
authors.forename: Shengnian
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000235:genetics; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006801:Humans; D008745:Methylation; D008875:Middle Aged; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018180:Thrombomodulin; D006710:Homocysteine
keywords: Cerebral infarction; DNA methylation; Homocysteine; Thrombomodulin