Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University of Bochum, Georgstr. 11, 32545, Bad Oeynhausen, NRW, Germany,
Inflamm Res. 2014 Apr;63(4):267-76. doi: 10.1007/s00011-013-0695-z. Epub 2013 Dec 8.
The coxsackie and adenovirus receptor (CAR) mediates the entry of coxsackievirus B (CVB) and adenovirus into host cells and is, therefore, a key determinant for the molecular pathogenesis of viral diseases such as myocarditis. The aim was to investigate the influence of HMG-CoA reductase inhibitor lovastatin on CAR expression in endothelial cells.
Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of lovastatin (0.05-5 μmol/l) for up to 48 h. Alterations in CAR expression were examined by quantitative real-time PCR (qRT-PCR) and flow cytometry. In addition, after treatment with 1 μmol/l lovastatin for 48 h, HUVECs were infected for 8 h with CVB3 and virus replication was detected by qRT-PCR using viral-specific TaqMan probes.
We found that lovastatin decreases CAR mRNA expression by up to 80% (p < 0.01) and CAR protein expression by up to 19% (p < 0.01), in a concentration-dependent manner. Moreover, virus replication of CVB3 was significantly inhibited after lovastatin treatment (p < 0.05). The signaling mechanism of CAR down-regulation by lovastatin depends on the Rac1/Cdc42 pathway.
This study shows for the first time that lovastatin reduces the expression of CAR and subsequently the replication of CVB3 in HUVECs.
柯萨奇病毒和腺病毒受体（CAR）介导柯萨奇病毒 B（CVB）和腺病毒进入宿主细胞，因此是病毒病（如心肌炎）分子发病机制的关键决定因素。目的是研究 HMG-CoA 还原酶抑制剂洛伐他汀对内皮细胞中 CAR 表达的影响。
将人脐静脉内皮细胞（HUVEC）暴露于不同浓度的洛伐他汀（0.05-5 μmol/l）中长达 48 小时。通过定量实时 PCR（qRT-PCR）和流式细胞术检测 CAR 表达的变化。此外，用 1 μmol/l 洛伐他汀处理 48 小时后，用 CVB3 感染 HUVEC 8 小时，并用病毒特异性 TaqMan 探针通过 qRT-PCR 检测病毒复制。
我们发现洛伐他汀以浓度依赖的方式使 CAR mRNA 表达降低高达 80%（p < 0.01），使 CAR 蛋白表达降低高达 19%（p < 0.01）。此外，洛伐他汀处理后 CVB3 的病毒复制明显受到抑制（p < 0.05）。CAR 下调的信号机制依赖于 Rac1/Cdc42 途径。
本研究首次表明，洛伐他汀降低了 HUVEC 中 CAR 的表达，随后降低了 CVB3 的复制。
