Expression of Membrane Bound O-Acyltransferase Domain Containing 7 after Myocardial Infarction and its Role in Lipid Metabolism in vitro.
Expression of Membrane Bound O-Acyltransferase Domain Containing 7 after Myocardial Infarction and its Role in Lipid Metabolism in vitro.
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DOI：
10.7150/ijms.70614
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发表时间：
2022
影响因子：
3.6
通讯作者：
Yang, Ping
中科院分区：
文献类型：
--
作者：
Li, Xiangdong;Wang, Zhiyuan;Meng, Heyu;Meng, Fanbo;Yang, Ping
背景：之前对三名急性心肌梗塞 (AMI) 患者外周血白细胞的微阵列分析表明，与对照相比，含有 7 (MBOAT7) 的膜结合邻酰基转移酶结构域的表达升高。为了进一步验证这些发现，我们研究了更多的患者并在体外探索了可能的机制。目的：研究AMI后白细胞中MBOAT7表达的变化，并探讨MBOAT7与体外肝细胞脂质代谢途径的关系。方法：从中国东北地区的汉族人群中招募 90 名 AMI 患者和 90 名对照者。 RT-荧光PCR用于测量MBOAT7 mRNA水平。构建MBOAT7干扰和过表达载体并转染至L-02肝细胞中，并通过RT-qPCR和蛋白质印迹检查表达。通过RT-qPCR研究脂质代谢途径中SCAP、LDLR、HMGCR、ACAT1、ABCA1、SREBP1、ACC、FAS、SCD和PPARγ的表达。通过 ELISA 测量甘油三酯和胆固醇水平。结果：发现AMI患者白细胞中MBOAT7 mRNA水平升高。肝细胞成功转染，沉默组 MBOAT7 mRNA 水平减弱（对照为 0.41±0.04 vs 1.01±0.07，P=0.0019 <0.01），过表达细胞中 MBOAT7 mRNA 水平升高（对照为 23.29±0.39 vs 1.00±0.06，P <0.0001）。这些结果通过蛋白质印迹得到证实。脂质代谢相关基因的表达因 MBOAT7 表达而改变。 MBOAT7 沉默后甘油三酯水平增加（对照为 118.40 ± 2.26 vs 70.54 ± 0.25，P<0.0001），胆固醇水平也增加（628.30 ± 8.89 vs 544.70 ± 11.04，P = 0.0041），但在 MBOAT7 过表达时没有改变。结论：MBOAT7不通过脂肪酸合成和分解途径影响肝细胞内甘油三酯的代谢。外周血中MBOAT7水平可作为急性心肌梗死的标志物，但不能作为调节脂质代谢的单一治疗靶点。
Background: Previous microarray analysis on peripheral blood leukocytes from three patients with acute myocardial infarction (AMI) showed that elevated expression of membrane bound o-acyltransferase domain containing 7(MBOAT7) relative to control. To further verify these findings, we investigated more patients and explored the possible mechanisms in vitro. Objective: To study alterations in MBOAT7 expression in leukocytes after AMI, and to explore the relationship between MBOAT7 and lipid metabolism pathways in hepatocytes in vitro. Methods: Ninety patients with AMI and 90 controls were recruited from the Han population in Northeast China. RT-fluorescent PCR was used to measure MBOAT7 mRNA levels. MBOAT7 interference and overexpression vectors were constructed and transfected into L-02 hepatocytes and expression was examined by RT-qPCR and western blotting. The expression of SCAP, LDLR, HMGCR, ACAT1, ABCA1, SREBP1, ACC, FAS, SCD, and PPARγ in the lipid metabolism pathway were investigated by RT-qPCR. Triglyceride and cholesterol levels were measured by ELISA. Results: It was found that MBOAT7 mRNA levels were elevated in the leukocytes of patients with AMI. Hepatocytes were successfully transfected, shown by attenuated MBOAT7 mRNA levels in the silenced group (0.41±0.04 vs 1.01±0.07 for control, P=0.0019 <0.01) and raised levels in the overexpressing cells (23.29±0.39 vs 1.00±0.06 for control, P <0.0001). These results were confirmed by western blotting. Expression of the lipid metabolism-related genes was altered in response to MBOAT7 expression. Triglyceride levels increased after MBOAT7 silencing (118.40 ± 2.26 vs 70.54 ± 0.25 for control, P<0.0001), as did those of cholesterol (628.30 ± 8.89 vs 544.70 ± 11.04, P = 0.0041) but were not altered on MBOAT7 overexpression. Conclusion: MBOAT7 did not affect the metabolism of triglycerides in hepatocytes through fatty acid synthesis and decomposition pathways. The MBOAT7 level in the peripheral blood can be used as a marker for acute myocardial infarction but cannot be used as a single therapeutic target to regulate lipid metabolism.
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通讯作者：
Mann JP