Cytomegalovirus infection causes an increase of arterial blood pressure.
Cytomegalovirus infection causes an increase of arterial blood pressure.
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DOI：
10.1371/journal.ppat.1000427
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发表时间：
2009-05
期刊：
影响因子：
6.7
通讯作者：
Crumpacker CS
中科院分区：
文献类型：
--
作者：
Cheng J;Ke Q;Jin Z;Wang H;Kocher O;Morgan JP;Zhang J;Crumpacker CS
巨细胞病毒(CMV)感染是一种常见的成人感染(全球血清阳性率为60%-99%)，与心血管疾病有关，与高血压和动脉粥样硬化等危险因素一致。一些病毒感染与高血压有关，包括人类疱疹病毒8型(HHV-8)和艾滋病毒-1。病毒感染如何导致高血压或血压升高的机制尚未确定。在这份报告中，巨细胞病毒感染作为血压升高和形成动脉粥样硬化斑块的原因进行了研究。利用体内小鼠模型和体外分子生物学分析，我们发现巨细胞病毒单独感染引起动脉血压显著升高(p<；0.01∼0.05)，通过微尖导管技术测量。这种由小鼠巨细胞病毒(MCMV)引起的血压升高与组织学分析定义的主动脉中动脉粥样硬化斑块的形成无关。套式聚合酶链式反应检测到病毒感染小鼠血管标本中可检测到MCMV DNA，而对照组小鼠血管中未检测到MCMV DNA。酶联免疫吸附试验显示，巨噬细胞病毒可显著增加小鼠血清中促炎细胞因子IL-6、肿瘤坏死因子-α和单核细胞趋化蛋白-1的表达。通过实时定量逆转录聚合酶链式反应(Q-RT-PCR)和Western印迹检测，我们发现CMV以感染剂量依赖的方式刺激人和鼠细胞肾素的表达。共染色和免疫荧光显微镜分析表明，MCMV感染在单细胞水平上刺激肾素的表达。进一步用ELISA法检测小鼠血清和动脉组织中的血管紧张素Ⅱ(Ang II)，发现MCMV感染后Ang II的表达增加。与小鼠实验结果一致，人巨细胞病毒(HCMV)感染血管内皮细胞(EC)以一种非裂解性感染的方式诱导肾素表达。病毒复制动力学和空斑形成分析表明，CMV在EC的活跃、持续感染和病毒基因的表达可能是其分子机制的基础。这些结果表明，巨细胞病毒感染是动脉血压升高的危险因素，也是动脉粥样硬化的辅助因素。EC的病毒持续感染可能是其发病机制之一。控制CMV感染可以控制心血管系统中的高血压和动脉粥样硬化。巨细胞病毒(CMV)感染与心血管疾病有关。然而，确切的机制仍有待确定。使用小鼠模型和细胞培养分析，我们发现CMV感染本身就会导致血压升高。此外，巨细胞病毒感染会增加高胆固醇饮食引起的血压升高。然而，CMV感染本身并不会导致动脉粥样硬化。然而，CMV感染加上高胆固醇饮食，会导致与心脏相连的主要动脉形成典型的动脉粥样硬化斑块。进一步的研究表明，CMV感染以一种持续感染的方式诱导血液和血管细胞中肾素和血管紧张素II(Ang II)的表达。已知肾素和血管紧张素II的表达增加会导致人类血压升高或高血压。病毒基因的表达和病毒持续感染血管内皮细胞导致肾素和血管紧张素Ⅱ等炎性细胞因子表达增加，可能是CMV感染引起血压升高的分子机制。
Cytomegalovirus (CMV) infection is a common infection in adults (seropositive 60–99% globally), and is associated with cardiovascular diseases, in line with risk factors such as hypertension and atherosclerosis. Several viral infections are linked to hypertension, including human herpes virus 8 (HHV-8) and HIV-1. The mechanisms of how viral infection contributes to hypertension or increased blood pressure are not defined. In this report, the role of CMV infection as a cause of increased blood pressure and in forming aortic atherosclerotic plaques is examined. Using in vivo mouse model and in vitro molecular biology analyses, we find that CMV infection alone caused a significant increase in arterial blood pressure (ABp) (p<0.01∼0.05), measured by microtip catheter technique. This increase in blood pressure by mouse CMV (MCMV) was independent of atherosclerotic plaque formation in the aorta, defined by histological analyses. MCMV DNA was detected in blood vessel samples of viral infected mice but not in the control mice by nested PCR assay. MCMV significantly increased expression of pro-inflammatory cytokines IL-6, TNF-α, and MCP-1 in mouse serum by enzyme-linked immunosorbent assay (ELISA). Using quantitative real time reverse transcriptase PCR (Q-RT-PCR) and Western blot, we find that CMV stimulated expression of renin in mouse and human cells in an infectious dose-dependent manner. Co-staining and immunofluorescent microscopy analyses showed that MCMV infection stimulated renin expression at a single cell level. Further examination of angiotensin-II (Ang II) in mouse serum and arterial tissues with ELISA showed an increased expression of Ang II by MCMV infection. Consistent with the findings of the mouse trial, human CMV (HCMV) infection of blood vessel endothelial cells (EC) induced renin expression in a non-lytic infection manner. Viral replication kinetics and plaque formation assay showed that an active, CMV persistent infection in EC and expression of viral genes might underpin the molecular mechanism. These results show that CMV infection is a risk factor for increased arterial blood pressure, and is a co-factor in aortic atherosclerosis. Viral persistent infection of EC may underlie the mechanism. Control of CMV infection can be developed to restrict hypertension and atherosclerosis in the cardiovascular system. Cytomegalovirus (CMV) infection is associated with cardiovascular diseases. The exact mechanisms, however, remain to be defined. Using both mouse model and cell culture analyses, we find that CMV infection alone causes an increase in blood pressure. Additionally, CMV infection augments the increased blood pressure induced by a high cholesterol diet. CMV infection alone, however, does not cause atherosclerosis in aortas. CMV infection along with a high cholesterol diet, however, causes the classic atherosclerotic plaque formation in the main artery connected to the heart. Further studies show that CMV infection induces renin and angiotensin II (Ang II) expression in blood and in vessel cells, in a persistent infection manner. An increased expression of renin and Ang II has been known to cause an increase in blood pressure or hypertension in humans. Expression of viral genes and viral persistent infection of blood vessel endothelial cells resulting in an increased expression of inflammatory cytokines, including renin and Ang II, may underpin the molecular mechanism by which CMV infection induces an increase in blood pressure.
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影响因子：
15.3
作者：
Daley, Eleen;Emson, Claire;Guignabert, Christophe;Malefyt, Rene de Waal;Louten, Jennifer;Kurup, Viswanath P.;Hogaboam, Cory;Taraseviciene-Stewart, Laimute;Voelkel, Norbert F.;Rabinovitch, Marlene;Grunig, Ekkehard;Grunig, Gabriele
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影响因子：
5.4
作者：
Fish, KN;Soderberg-Naucler, C;Nelson, JA
通讯作者：
Nelson, JA
影响因子：
5.3
作者：
Hsich, E;Zhou, YF;Epstein, SE
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