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Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure

By Jilin Cheng, Qingen Ke, Zhuang Jin, Haibin Wang, Olivier Kocher, James P. Morgan, Jielin Zhang and Clyde S. Crumpacker

Abstract

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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2673691
Provided by: PubMed Central
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    Citations

    1. (2000). A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates.
    2. (2006). Analysis of the human cytomegalovirus genomic region from UL146 through UL147A reveals sequence hypervariability, genotypic stability, and overlapping transcripts.
    3. (1996). Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy.
    4. (2000). Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation.
    5. (1998). Cellular localization of latent murine cytomegalovirus.
    6. (2007). Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo.
    7. (2005). Cocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion molecules.
    8. (2005). Comparison of coronary and aortic atherosclerosis in youth from Japan and the USA.
    9. (2001). Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice.
    10. (2005). Cytomegalovirus infection of the heart is common in patients with fatal myocarditis.
    11. (1998). Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell contact and during neutrophil transendothelial migration.
    12. (1995). Detection of human cytomegalovirus DNA, RNA, and antibody in normal donor blood.
    13. (2000). Diagnostic Implications of Human Cytomegalovirus Immediate Early-1 and pp67 mRNA Detection in Whole-Blood Samples from Liver Transplant Patients Using Nucleic Acid Sequence-Based Amplification.
    14. (2000). Disruption of PML-associated nuclear bodies by IE1 correlates with efficient early stages of viral gene expression and DNA replication in human cytomegalovirus infection.
    15. (2006). Effects of normal, pre-hypertensive, and hypertensive blood pressure levels on progression of coronary atherosclerosis.
    16. (2005). Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice.
    17. (2004). Enhanced cytomegalovirus infection in atherosclerotic human blood vessels.
    18. (2003). Expression of human herpesvirus 8 in primary pulmonary hypertension.
    19. (1999). Frequency and factors associated with cardiomyopathy in patients with human immunodeficiency virus infection in an inner-city hospital.
    20. (1991). Herpesvirus infection: an overview of the clinical manifestations.
    21. (2000). High-fat diet elevates blood pressure and cerebrovascular muscle Ca(2+) current.
    22. (2003). Historical perspective of the renin-angiotensin system.
    23. (2002). Human cytomegalovirus and human umbilical vein endothelial cells: restriction of primary isolation to blood samples and susceptibilities of clinical isolates from other sources to adaptation.
    24. (1998). Human cytomegalovirus persistently infects aortic endothelial cells.
    25. (2003). Human cytomegalovirus seropositivity is associated with impaired vascular function.
    26. (2001). Hypertension status is the major determinant of carotid atherosclerosis: a community-based study in Taiwan.
    27. (2007). IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension.
    28. (2006). Immune activation following cytomegalovirus infection: more important than direct viral effects in cardiovascular disease?
    29. (1999). Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebocontrolled study.
    30. (2008). Increased mortality in long-term intensive care patients with active cytomegalovirus infection.
    31. (2002). Inflammation, malnutrition and atherosclerosis in end-stage renal disease: a global perspective.
    32. (2008). Involvement of tumor necrosis factor-alpha in angiotensin II-mediated effects on salt appetite, hypertension, and cardiac hypertrophy.
    33. (1998). Lack of evidence for a pathogenic role of Chlamydia pneumoniae and cytomegalovirus infection in coronary atheroma formation.
    34. (1990). Morphology, physiology, and molecular biology of renin secretion.
    35. (2003). Multiple infections and subsequent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE)
    36. (1991). National Eye Institute issues clinical alert about CMV retinitis in AIDS.
    37. (1995). Primary pulmonary hypertension and the human immunodeficiency virus. Report of two cases and a review of the literature.
    38. (1998). Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis.
    39. (2008). Pulmonary arterial remodeling induced by a Th2 immune response.
    40. (2006). RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney.
    41. (2006). RAS inhibition in hypertension.
    42. (2006). Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study.

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