Author + information
- Cong Guangzhi,
- Shaobin Jia and
- Yan Ru
Background: Hyperhomocystienmia(HHcy) is a strong risk factor for cardiovascular disease and it has been demonstrated in mediating the pathogenicity of atherosclerosis via an epigenetic mechanism. But the underlying mechanism remains unclear. Here, we tested the hypothesis whether the effect of HHcy on atherosclerosis is involved in epigenetic regulation of histone methylation.
Methods: Four week old male ApoE double knock mice were received a control(n= 12)or methionine (2%) diet(n=12) to induce HHcy for 16 weeks. Plasma homocysteine, lipid profile, stability of atherosclerotic plaques and histone methylation(dimethylated histone H3 lysine 4 and dimethylated histone H3 lysine 9) in the aortic root region were analyzed. We also detected the alternation of histone methylation and histone methyltransferase(SUV39H1, SUV39H1 and ESET)in Raw 264.7 cell line after challenged with homocysteine by western blot.
Results: Plasma homocysteine levels and lesion size were significantly increased in methionine diet groups in both en face aorta and aortic valve sections when compared with control group. Interestingly, HHcy mice also presented increased lipid and macrophage content but without alternation of intraplaque smooth muscle and collagen staining, which suggest formation of unstable atherosclerotic plaques. The immunostaining of dimethylated histone H3 lysine 9 but not dimethylated histone H3 lysine 4 was decreased in the advanced lesion group fed the HM diet compared with the control group. A decreased expression of dimethylated histone H3 lysine 9 also was observed in Raw 264.7 cell line after challenged with homocysteine. The expression of histone methyltransferase ESET but not SUV39H1 an dSUV39H1, which responsible for dimethylated histone H3 lysine 9, was depression when challenged with homocysteine.
Conclusions: Alternation of global dimethylated histone H3 lysine 9 is associated with formation of unstable plaque in hypehomocystinemic ApoE double knock mice.
Poster Hall, Hall C
Sunday, March 19, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Insights Into Ischemic Heart Disease: Stable to Erosive Plaques
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1295-301
- 2017 American College of Cardiology Foundation