The effects of hyperhomocysteinemia on myocardial endoplasmic reticulum stress in ApoE-/-mice

ZHOU Long-xia; ZHAO Li; CHEN Jiu-kai; YANG An-ning; LIU Xian-mei; WANG Yan-hua; JIANG Yi-deng; CAO Jun

Abstract：Objective To investigate the effects of hyperhomocysteinemia ( HHcy ) on myocardial endoplasmic reticulum stress ( ERS) in ApoE-/-mice and its possible mechanism.Methods Thirty-six 5 -week old ApoE-/-C57BL/6J mice were randomly divided into three groups, including ApoE-/-control group, ApoE-/-HHcy group and the intervention group.Twelve 5-week old normal C57BL/6J mice were served as normal group.After 20 weeks of feed-ing, the aortae were separated for HE stain and observation of aortic plaque.GRP78, CHOP and Caspase-12 mRNA lev-els were determined by qRT-PCR.The methylation status of GRP78 and CHOP were studied using the nest touch down methylation specific polymerase chain reaction ( ntMS-MSP) .Results No significant aortic plaque was observed in ei-ther normal group or ApoE-/-control group.In the ApoE-/-HHcy group, the aortic plaque areas were greater, breaking into the aortic lumina, which were alleviated in the intervention group.The mRNA levels of GRP78, CHOP and Caspase-12 in the ApoE-/-HHcy group were significantly higher than those in ApoE-/-control group(P<0.05,P<0.01), while they were significantly down-regulated in the intervention group(P<0.05,P<0.01).GRP78 and CHOP DNA methylation levels were significantly lowered in the ApoE-/-HHcy group(P<0.01,P<0.01),while significanty higher in the intervention group(P<0.05,P<0.05).Conclusion HHcy may affect Myocardial ERS via changing DNA methy-lation levels, then lead to apoptosis.Earlier folic acid and VB12 interference can effectively reduce the myocardial ERS and apoptosis.