Li Gang, Wu Xiao-wei, Lu Wei-hua, Ai Rong, Chen Fang, Tang Zhong-zhi
Emergency Department, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430074, China.
BMC Cardiovasc Disord. 2014 Oct 18;14:145. doi: 10.1186/1471-2261-14-145.
Gamma-glutamyl transpeptidase (GGT) is now considered to be one of the risk factors for cardiovascular disease. However, whether statins can alter GGT levels in arterial atheromatous plaque has not yet been studied. Therefore, the aim of this study is to determine whether statins can effectively decrease the expression of GGT in arterial atheromatous plaques.
We randomly divided 45 apolipoprotein E-knockout (ApoE KO) male mice into three groups: normal diet (ND) group,high-cholesterol diet (HCD) group and high-cholesterol diet and atorvastatin (HCD + Ato) group. We fed high-cholesterol food to the HCD and HCD + Ato group. After eight weeks, atorvastatin 5 mg•kg-1•d-1 was given to HCD + Ato group mice. The serum GGT-1, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell-adhesion molecule-1 (VCAM-1) levels were measured at end of 16 weeks by using ELISA methods. The expressions of GGT-1, ICAM-1 and VCAM-1 in aorta were measured by RT-PCR and Western Blot.
The ApoE KO mice with HCD were associated with a marked increase in plasma lipid, inflammatory factors, GGT-1, ICAM-1 and VCAM-1. The expressions of GGT-1, ICAM-1 and VCAM-1 in HCD aortic tissue were increased. At the HCD + Ato group were treated with atorvastatin, the levels of lipid, GGT-1, ICAM-1 and VCAM-1 were suppressed. Meanwhile, the expressions of GGT-1, ICAM-1 and VCAM-1 were significantly decreased in the whole aorta plaques.
The effect of statins on the expression of GGT in aorta plaque was firstly observed in animal model. The research shows that statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques.
γ-谷氨酰转肽酶(GGT)现被认为是心血管疾病的危险因素之一。然而,他汀类药物是否能改变动脉粥样斑块中的GGT水平尚未得到研究。因此,本研究的目的是确定他汀类药物是否能有效降低动脉粥样斑块中GGT的表达。
我们将45只载脂蛋白E基因敲除(ApoE KO)雄性小鼠随机分为三组:正常饮食(ND)组、高胆固醇饮食(HCD)组和高胆固醇饮食加阿托伐他汀(HCD + Ato)组。我们给HCD组和HCD + Ato组喂食高胆固醇食物。八周后,给HCD + Ato组小鼠给予5 mg•kg-1•d-1的阿托伐他汀。在第16周结束时,采用酶联免疫吸附测定(ELISA)方法测量血清GGT-1、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)水平。通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法(Western Blot)测量主动脉中GGT-1、ICAM-1和VCAM-1的表达。
HCD喂养的ApoE KO小鼠血浆脂质、炎症因子、GGT-1、ICAM-1和VCAM-1显著增加。HCD主动脉组织中GGT-1、ICAM-1和VCAM-1的表达增加。在HCD + Ato组用阿托伐他汀治疗后,脂质、GGT-1、ICAM-1和VCAM-1水平受到抑制。同时,整个主动脉斑块中GGT-1、ICAM-1和VCAM-1的表达显著降低。
在动物模型中首次观察到他汀类药物对主动脉斑块中GGT表达的影响。研究表明,他汀类药物可显著降低主动脉粥样硬化斑块中GGT的表达。