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Hyperhomocysteinemia accelerates atherosclerosis and induces inflammatory monocyte differentiation in hyperglycemic mice
Author(s) -
Fang Pu,
Zhang Daqing,
Jiang Xiaohua,
Yang Xiaofeng,
Wang Hong
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.991.6
Subject(s) - endocrinology , medicine , hyperhomocysteinemia , bone marrow , inflammation , diabetes mellitus , apolipoprotein e , apolipoprotein b , spleen , genetically modified mouse , monocyte , homocysteine , transgene , biology , cholesterol , gene , biochemistry , disease
Cardiovascular events are increased in patients with diabetes mellitus (DM) and hyperhomocysteinemia (HHcy). However, the underlying mechanism is unclear. In this study, we examined the role and mechanisms of HHcy on atherosclerosis under hyperglycemic condition. We established an atherosclerosis‐susceptible mouse model with both severe HHcy and hyperglycemia in which the mouse Cystathionine β‐Synthase ( Cbs ) and Apolipoprotein E ( ApoE ) genes are deficient and an inducible human CBS transgene is introduced (Tg‐hCBS ApoE −/− Cbs −/− mice). HHcy aggravated metabolic abnormalities in the hyperglycemic mice, including increased urine secretion, increased water consumption, increased blood glucose level and decreased body weight. Increased atherosclerotic lesions were also found in the hyperglycemic HHcy mice. Furthermore, HHcy increased inflammatory Ly6C hi MC in peripheral blood, spleen and bone marrow of the hyperglycemic mice. This may be due to hypomethylation since plasma level of Hcy is negatively associated with SAM/SAH ratio in mice. In cultured mouse primary splenocytes, L‐Hcy with D‐glucose induced Ly6C + subset. These Ly6C + MCs exhibited increased TNF‐α production, confirming their inflammatory properties. We concluded that HHcy promotes differentiation of inflammatory MC subset and contributes to atherosclerotic lesions in hyperglycemia. This study is supported by a NIH grant.