NAD(P)H oxidase and eNOS play differential roles in cytomegalovirus infection-induced microvascular dysfunction

Leskov, Igor L.; Whitsett, Jennifer; Vásquez‐Vivar, Jeannette; Stokes, Karen Y.

doi:10.1016/j.freeradbiomed.2011.09.039

Cited by 15 publications

(7 citation statements)

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“…Landmesser et al [ 27 ] reported that CMV infections can result in increased levels of oxidative stress and inflammation, which have been linked to endothelial damage in EH [ 28 ]. In an animal study, CMV infection was shown to reduce nitric oxide (NO) bioavailability in endothelial cells and activate nicotinamide adenine dinucleotide phosphate oxidase, which resulted in arteriolar dysfunction [ 29 ]. Recent evidence indicates that CMV infection impairs endothelial NO synthase (eNOS) function and causes endothelial damage [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

Tang

Liu

et al. 2014

Med Sci Monit

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BackgroundWe aimed to study the association between cytomegalovirus (CMV) infection and hypertension in Kazakh and Han populations from Xinjiang Province, China.Material/MethodsWe analyzed data on 800 Kazakhs (467 hypertension patients and 333 healthy control participants) and 800 Hans (482 hypertension patients and 318 healthy control participants) aged 18–84 years old. ELISA and real-time quantitative PCR coupled with restriction fragment length polymorphism analysis were applied for determining CMV infection and glycoprotein B (gB) genotypes, respectively.ResultsSerologic evidence of CMV infection was obtained for 95.4% and 90.1% of the Kazakhs and Hans, respectively. The CMV seroprevalence rates among the Kazakh and Han participants with hypertension were 96.8% and 89.8%, respectively. Multiple logistic regression analyses revealed statistically significant independent associations between CMV seropositivity and hypertension in Kazakh males and between CMV antibody titers and hypertension in Hans; significant relationships also existed between CMV antibody titers and blood pressure in Hans. In Kazakhs, 3 CMV gB genotypes were identified: gB2 and genotype mixtures gB1+gB2 and gB2+gB3. In Hans, 4 CMV gB genotypes were identified: gB1, gB2, gB1+gB2, and gB2+gB3. Of the 4 studied genotypes, gB2+gB3 showed a significant independent association with hypertension in Kazakh females.ConclusionsCMV infection is associated with essential hypertension in Kazakh males and Hans in Xinjiang. CMV seropositivity is associated with hypertension in Kazakh males, and CMV antibody titers are associated with blood pressure and hypertension in Han males and females. Moreover, the CMV gB2+gB3 genotype mixture is associated independently with essential hypertension in Kazakh females.

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Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

Tang

Liu

et al. 2014

Med Sci Monit

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“…In contrast, it is essential to compensate for vascular dysfunction in systemic (mesenteric) vascular beds that regulate blood pressure and cardiovascular function (36). The increase in ME-dependent vasodilation in mesenteric arteries from aged latently infected mice does not appear to be dependent on NOS or prostaglandin activity or an increase in smooth muscle sensitivity to NO, similar to findings in cremaster arteries from young persistently CMV-infected mice (31). It is therefore likely to be due to changes in other endothelium-derived hyperpolarizing factors that may contribute to ME-induced vasodilation (4).…”

Section: Discussionmentioning

confidence: 71%

“…and CMV infections (6,14,17,19,28,31) are associated with increased blood pressure, vascular stiffness, and vascular dysfunction. The systemic vasculature in aging may compensate for the combined insults of aging and infection with increased endothelium-dependent vasodilation, even in the presence of a latent, not active, mCMV infection (12).…”

Section: Discussionmentioning

confidence: 99%

Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections

Gombos

Brown

Teefy

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Gombos RB, Brown JC, Teefy J, Gibeault RL, Conn KL, Schang LM, Hemmings DG. Vascular dysfunction in young ec50, mid-aged and aged mice with latent cytomegalovirus infections. Am J Physiol Heart Circ Physiol 304: H183-H194, 2013. First published November 2, 2012; doi:10.1152/ajpheart.00461.2012.-Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active and latent phases throughout life. We and others have shown vascular dysfunction during active mouse CMV (mCMV) infections. Few studies have examined changes in physiology during latent CMV infections, particularly vascular responses or whether the negative effects of aging on vascular function and fertility will be exacerbated under these conditions. We measured vascular responses in intact mesenteric and uterine arteries dissected from young, mid-aged, and aged latently mCMV-infected (mCMV genomes are present but infectious virus is undetectable) and agematched uninfected mice using a pressure myograph. We tested responses to the ␣ 1-adrenergic agonist phenylephrine, the nitric oxide donor sodium nitroprusside, and the endothelium-dependent vasodilator methacholine. In young latently mCMV-infected mice, vasoconstriction was increased and vasodilation was decreased in mesenteric arteries, whereas both vasoconstriction and vasodilation were increased in uterine arteries compared with those in age-matched uninfected mice. In reproductively active mid-aged latently infected mice, mesenteric arteries showed little change, whereas uterine arteries showed greatly increased vasoconstriction. These vascular effects may have contributed to the decreased reproductive success observed in mid-aged latently mCMV-infected compared with age-matched uninfected mice (16.7 vs. 46.7%, respectively). In aged latently infected mice, vasodilation is increased in mesenteric and uterine arteries likely to compensate for increased vasoconstriction to mediators other than phenylephrine. The novel results of this study show that even when active mCMV infections become undetectable, vascular dysfunction continues and differs with age and artery origin. uterine arteries; mesenteric arteries; infertility; vascular function; pressure myograph HUMAN CYTOMEGALOVIRUS (HCMV) is a member of the ␤-Herpesviridae family (50). In the human population, it infects 40 to 80% of individuals (10). Although in the general population it is thought to be mostly asymptomatic, infection has been associated with tumorigenesis, transplant rejection, vascular diseases such as atherosclerosis and restenosis, and increased mortality and hypertension (9,19,23,26,33,62,64). The mechanisms whereby HCMV infections result in vasculopathy are still unclear.

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“…Results from a population-based study evaluating cardiovascular risk factors and seropositivity to various pathogens [24] showed that antibody titers against CMV were not a marker for prevalence or incidence of atherosclerosis. However, evidence from animal studies points to an active role of CMV in cardiovascular disease including atherosclerosis [12, 25–30]. It has been suggested that the contribution of CMV to atherosclerosis is through the initiation and sustainment of inflammatory processes [26–28] induced by the virus.…”

Section: Discussionmentioning

confidence: 99%

Murine Cytomegalovirus (MCMV) Infection Upregulates P38 MAP kinase in Aortas of Apo E KO Mice: a Molecular Mechanism for MCMV-Induced Acceleration of Atherosclerosis

Tang-Feldman

Lochhead

et al. 2012

J. of Cardiovasc. Trans. Res.

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Multiple studies suggest an association between cytomegalovirus (CMV) infection and atherogenesis; however, the molecular mechanisms by which viral infection might exacerbate atherosclerosis are not well understood. Aortas of MCMV-infected and uninfected Apo E knockout (KO) mice were analyzed for atherosclerotic lesion development and differential gene expression. Lesions in the infected mice were larger and showed more advanced disease compared to the uninfected mice. Sixty percent of the genes in the MAPK pathway were upregulated in the infected mice. p38 and ERK 1/2 MAPK genes were 5.6- and 2.0-fold higher, respectively, in aortas of infected vs. uninfected mice. Levels of VCAM-1, ICAM-1, and MCP-1 were ~2.0–2.6-fold higher in aortas of infected vs. uninfected mice. Inhibition of p38 with SB203580 resulted in lower levels of pro-atherogenic molecules and MCMV viral load in aortas of infected mice. MCMV-induced upregulation of p38 may drive the virus-induced acceleration of atherogenesis observed in our model.

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NAD(P)H oxidase and eNOS play differential roles in cytomegalovirus infection-induced microvascular dysfunction

Cited by 15 publications

References 64 publications

Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

Human Cytomegalovirus Infection is Associated with Essential Hypertension in Kazakh and Han Chinese Populations

Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections

Murine Cytomegalovirus (MCMV) Infection Upregulates P38 MAP kinase in Aortas of Apo E KO Mice: a Molecular Mechanism for MCMV-Induced Acceleration of Atherosclerosis

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