Copyright © 2005, European Society of Cardiology
HCMV infection of human vascular smooth muscle cells leads to enhanced expression of functionally intact PDGF β-receptor
aDepartment of Internal Medicine II, Ulm University Medical Center, Ulm, Germany
bDepartment of Virology, Ulm University Medical Center, Ulm, Germany
cDepartment of Cardiology, University of Maastricht, Maastricht, The Netherlands
* Corresponding author. Department of Cardiology, University Hospital Maastricht, P. Debyelaan 25, PO Box 5800, Maastricht 6202 AZ, The Netherlands. Tel.: +31 43 387 5106; fax: +31 43 387 5104. Email address: j.waltenberger{at}cardio.azm.nl
Background: Cytomegaloviruses have been shown to promote atherogenesis in animal models. In humans, several epidemiological and clinical studies suggest involvement of the human cytomegalovirus (HCMV) in the development of atherosclerosis. HCMV is suspected to be associated with an enhanced restenosis rate and the occurrence of vasculopathies after solid organ transplantation. However, knowledge about the cellular and molecular bases of these findings is very limited.
Methods and results: Human coronary artery smooth muscle cells (HCASMC) were successfully infected with HCMV in vitro. Infection of HCASMC with all HCMV strains analyzed resulted in a substantial upregulation of the β-receptor of platelet-derived growth factor (PDGFR-β) expression as demonstrated by immunohistochemistry, immunofluorescence, FACS, and Western blot analysis. The amount of PDGFR-β protein present in HCASMC rapidly increased after 12 h of infection and this difference persisted for 72 h post-infection. We showed by quantitative FACS analysis that the extent of PDGFR-β upregulation differed significantly between the HCMV strains TB40E, Toledo, and AD169. The expression of insulin-like growth factor receptors as well as hepatocyte growth factor receptors, however, was downmodulated in HCMV-infected HCASMC. Most importantly, the HCMV-associated upregulation of PDGFR-β protein resulted in functionally intact receptors. A significantly higher increase of proliferative activity following stimulation with PDGF-BB was observed in HCMV-infected HCASMC compared to the uninfected control.
Conclusions: Our data suggest that HCMV directly activates the PDGF system, which could promote atherogenesis and restenosis by activation of smooth muscle cell proliferation and neointima formation.
KEYWORDS Growth factors; Atherosclerosis; Vascular smooth muscle cells; Cytomegalovirus; Platelet-derived growth factor
Time for primary review 18 days
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