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Direct inhibitory effects of Ganciclovir on ICAM-1 expression and proliferation in human coronary vascular cells

Rainer Voisard1, Ulrike Münder, Lutz von Müller

  • 1Department of Internal Medicine II-Cardiology, University of Ulm, Ulm, Germany. rainer@voisard.de

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
|December 21, 2010
PubMed
Abstract

Insights

Ganciclovir shows antiproliferative effects on coronary cells, partially due to cytotoxicity. Its impact on ICAM-1 expression and cell proliferation may be relevant in vivo for drug-eluting stents.

Area of Science:

  • Cardiovascular Research
  • Virology
  • Pharmacology

Background:

  • Human cytomegalovirus (HCMV) infection influences cardiovascular conditions like restenosis and atherosclerosis.
  • Ganciclovir treatment for HCMV infection has indirect benefits on these conditions.
  • This study investigates the direct effects of ganciclovir on key factors in coronary atherosclerosis.

Purpose of the Study:

  • To evaluate the direct impact of ganciclovir on intercellular adhesion molecule 1 (ICAM-1) expression.
  • To assess the direct impact of ganciclovir on endothelial and smooth muscle cell proliferation.
  • To determine the clinical relevance of ganciclovir's effects using SI/MPL-ratios.

Main Methods:

  • In vitro studies using cytoflow analysis on human umbilical vein endothelial cells (HUVEC), human coronary artery endothelial cells (HCAEC), and human coronary smooth muscle cells (HCMSMC).
  • Ganciclovir was administered at concentrations ranging from 0.05 to 5000 µg/mL.
  • Assessed TNF-α induced ICAM-1 expression, cell proliferation, and cytotoxic effects.

Main Results:

  • Ganciclovir exhibited slight but significant inhibition of ICAM-1 expression in all tested cell types.
  • Dose-dependent and significant antiproliferative effects of ganciclovir were observed across all cell types.
  • Cytotoxic effects partially contributed to the observed antiproliferative actions of ganciclovir.

Conclusions:

  • SI/MPL-ratios greater than 1 in HCAEC and HCMSMC suggest that ganciclovir's inhibitory effects on ICAM-1 and proliferation may occur in vivo.
  • These effects are likely relevant only with high local drug concentrations, such as those delivered by drug-eluting stents (DES).
  • Ganciclovir's direct cellular effects warrant consideration in the context of cardiovascular interventions.

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