Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10)

Shen, Ying H.; Zhang, Lin; Utama, Budi; Wang, Jian; Gan, Ye‐Hua; Wang, Xinwen; Chen, Li; Vercellotti, G. M.; Coselli, Joseph S.; Mehta, Jawahar L.; Wang, Xing Li

doi:10.1016/j.cardiores.2005.10.007

Cited by 45 publications

(38 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In human aortic endothelial cells, palmitic acid causes an upregulation of PTEN activity and transcription, which leads to inactivation of eNOS via the p38/Akt signaling pathway [32]. In addition, Akt-mediated eNOS activation of human aortic endothelial cells was inhibited by human cytomegalovirus via up-regulation of PTEN [33]. The expression of PTEN in the tibialis anterior muscle was up-regulated in mice under conditions of chronic diabetic/insulin resistance, suggesting the participation of PTEN [34].…”

Section: Discussionmentioning

confidence: 92%

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Seto

Lam

et al. 2010

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 92%

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Seto

Lam

et al. 2010

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

“…However, the specific underlying pathophysiological mechanisms linking HCMV with essential hypertension are yet to be defined. Human cytomegalovirus infection exerts an inhibitory effect on endothelial nitric oxide synthase activation, thereby reducing nitric oxide production, activating the stress-response signal P38-MAPK pathway, and upregulating phosphatase and tensin homolog, 21,22 leading to endothelial dysfunction. 23,24 Human cytomegalovirus infection stimulates renin and angiotensin II expression in human vascular endothelial cells, 39 enhancing NAD(P)H oxidase activity, and elicits the production of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

“…17 It has been implicated in several cardiovascular disorders, including atherosclerosis, coronary heart disease, and cardiac transplant arteriopathy. 18 -20 Some studies suggest an association between HCMV and cardiovascular disorders through impaired endothelial nitric oxide synthase function 21,22 and subsequent endothelial dysfunction, 23,24 resulting in reduced vascular dilation in vivo. However, direct links between HCMV infection, endothelial dysfunction, and essential hypertension remain undefined.…”

mentioning

confidence: 99%

Signature microRNA Expression Profile of Essential Hypertension and Its Novel Link to Human Cytomegalovirus Infection

et al. 2011

View full text Add to dashboard Cite

Background-Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension. Methods and Results-Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296 -5p, let-7e, and a human cytomegalovirus [HCMV]-encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296 -5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all PϽ0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112.Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%, Pϭ0.0005; 1870 versus 54 copies per 1 mL plasma, PϽ0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15; Pϭ0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46; PϽ0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27; PϽ0.0001, respectively). Conclusions-We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00420784. Key Words: cytomegalovirus Ⅲ hypertension Ⅲ interferon regulatory factor-1 Ⅲ microRNAs E ssential hypertension is a predisposing risk factor for stroke, myocardial infarction, congestive heart failure, and arterial aneurysm; it is also the leading cause of chronic renal failure. 1 Approximately 90% to 95% of hypertension, affecting Ͼ1 billion adults worldwide, is the essential hypertension subtype. 2 Discernment between essential and secondary hypertension is critical because the former has no precise cause and the latter has a clear cause usually remediable by a Clinical Perspective on p 184 microRNAs (miRNAs) are short, endogenous, noncoding RNAs that regulate gene expression at the posttranscriptional level by binding to the 3Ј untranslated regions (UTRs) of their target mRNAs. 7 Although dysregulation of miRNA expression is a feature of malignancies, 8 -10 research into miRNAs in biological processes reveals their regulation of immune cell development, 11 involvement in inflammatory response, 12 and critical participation...

show abstract

“…thase function (44,54), leading to endothelial dysfunction (17,42), measured in vivo as reduced dilation. However, direct links between HCMV, endothelial dysfunction, and vascular diseases remain undefined, and the effect of in vivo infections on vascular function in isolated arteries has not been examined.…”

mentioning

confidence: 99%

Impaired vascular function in mice with an active cytomegalovirus infection

Gombos

Wolan²,

McDonald³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Human cytomegalovirus (CMV) is implicated in vascular complications through endothelial dysfunction. However, the effect of in vivo infections on vascular function in isolated arteries has not been examined. In pregnancy, systemic and uterine vascular adaptations accommodate increased blood volume through several mechanisms, including decreased sensitivity to vasoconstrictors and increased production of endothelial-dependent vasodilators. We hypothesized that an active in vivo CMV infection would reduce vasodilation of isolated arteries to the endothelial-dependent vasodilator methacholine and increase vasoconstriction to the alpha(1)-adrenergic receptor agonist phenylephrine and that these CMV-induced changes would be accentuated in late pregnancy. A mouse CMV infection model was used to study vascular responses in isolated mesenteric and uterine arteries from nonpregnant and late pregnant mice. In the mouse, CMV is not transmitted to the fetus. Accordingly, there was no evidence of active infection in any fetus examined, even though an active infection was found in salivary glands, uterine and mesenteric arteries, and placentas. Contrary to our hypothesis, increased endothelial-dependent vasodilation was found in mesenteric arteries from infected compared with uninfected nonpregnant and pregnant mice These data implicate active CMV infections in hypotensive disorders. Similarly, increased vasodilation was found in uterine arteries from infected vs. uninfected nonpregnant mice. However, this was completely reversed in infected compared with uninfected late pregnant mice in which vasodilation in uterine arteries was significantly reduced. Uterine arteries from infected pregnant mice also showed increased vasoconstriction to phenylephrine. Maternal infection led to decreased placental weights but had no effect on fetal weights in late pregnancy. These novel data demonstrate abnormal systemic and uterine vascular responses during an active CMV infection in both nonpregnant and late pregnant mice. Importantly, despite reduced placental weights, fetal weights were maintained, suggesting effective intrauterine compensation in the mouse model.

show abstract

Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10)

Abstract: In summary, our findings suggest that inhibition of eNOS leading to endothelial dysfunction may be a basis of the pro-atherogenic effects of HCMV. Importantly, upregulation of PTEN and activation of stress signal p38 MAPK are involved in HCMV's inhibitory effects on eNOS activation.

Cited by 45 publications

References 53 publications

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Signature microRNA Expression Profile of Essential Hypertension and Its Novel Link to Human Cytomegalovirus Infection

Impaired vascular function in mice with an active cytomegalovirus infection

Contact Info

Product

Resources

About