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

Ying H. Shen, Lin Zhang, Budi Utama, Jian Wang, Yehua Gan, Xinwen Wang, Jing Wang, Li Chen, Greg M. Vercellotti, Joseph S. Coselli, Jawahar L. Mehta, Xing Li Wang

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Objectives: Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV) infection may play a role in the development of this disease. Diminished expression and/or activity of endothelial nitric oxide synthase (eNOS) are an early event in atherogenesis. In the current study, we investigated the effects of HCMV infection on eNOS activation in human aortic endothelial cells (HAECs). Methods and results: We found that HCMV inhibited eNOS phosphorylation/activation in HAECs. The signaling upstream of eNOS involving Akt and PDK1 were also suppressed by the HCMV infection. Moreover, HCMV infection increased the expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10). Silencing PTEN expression with specific siRNA reversed the inhibitory effects on eNOS activation in HCMV-infected cells indicating the involvement of PTEN in mediating HCMV's inhibitory effects. Next we observed that the activation of p38 MAPK stress signaling pathway mediates HCMV's effects on PTEN up-regulation and eNOS inactivation. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)502-511
Number of pages10
JournalCardiovascular Research
Volume69
Issue number2
DOIs
StatePublished - Feb 1 2006

Bibliographical note

Funding Information:
This project is supported by grants NIH/NHLBI R01-HL071608 to XLW and AHA-TX 0565134Y to YHS.

Keywords

  • Akt
  • Cytomegalovirus
  • PTEN
  • eNOS
  • p38 MAPK

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