Cytomegalovirus Infection Impairs the Nitric Oxide Synthase Pathway: Role of Asymmetric Dimethylarginine in Transplant Arteriosclerosis

Michael Weis, Thomas N. Kledal, Ken Y. Lin, Shyam N. Panchal, S. Z. Gao, Hannah A. Valantine, Edward S. Mocarski, John P. Cooke

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

Background-We hypothesized that cytomegalovirus (CMV) may contribute to the vasculopathy observed in cardiac allograft recipients by impairing the endothelial nitric oxide synthase pathway. We focused on asymmetric dimethylarginine (ADMA, the endogenous inhibitor of nitric oxide synthase) as a potential mediator of the adverse vascular effect of CMV. Methods and Results-Heart transplant recipients manifested elevated plasma ADMA levels compared with healthy control subjects. Transplant patients with CMV DNA-positive leukocytes had higher plasma ADMA concentrations and more extensive transplant arteriopathy (TA). Human microvascular endothelial cells infected with the CMV isolates elaborated more ADMA. The increase in ADMA was temporally associated with a reduction in the activity of dimethylarginine dimethylaminohydrolase (DDAH, the enzyme that metabolizes ADMA). Infected cultures showed high levels of oxidative stress with enhanced endothelial production of superoxide anion. Conclusion-CMV infection in human heart transplant recipients is associated with higher ADMA elevation and more severe TA. CMV infection in endothelial cells increases oxidative stress, impairs DDAH activity, and increases ADMA elaboration CMV infection may contribute to endothelial dysfunction and TA by dysregulation of the endothelial nitric oxide synthase pathway.

Original languageEnglish (US)
Pages (from-to)500-505
Number of pages6
JournalCirculation
Volume109
Issue number4
DOIs
StatePublished - Feb 3 2004

Keywords

  • Arteriosclerosis
  • Endothelium
  • Transplantation
  • Viruses

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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