Direct inhibitory effects of Ganciclovir on ICAM-1 expression and proliferation in human coronary vascular cells (SI/MPL-ratio: >1)

Abstract

SummaryBackgroundTreatment of the human cytomegalovirus (HCMV) infection with ganciclovir has beneficial indirect effects on the complex interactions of HCMV with restenosis, atherosclerosis, and transplant vascular sclerosis. The current study reports on direct effects of ganciclovir on expression of ICAM-1 and cell proliferation, key events of coronary atherosclerosis/restenosis. A potential clinical relevance of the data will be evaluated with the help of SI/MPL-ratio’s.Material/MethodsDefinition of the SI/MPL-ratio: relation between significant inhibitory effects in vitro/ex vivo and the maximal plasma level after systemic administration in vivo (ganciclovir: 9 μg/ml). Part I of the study investigated in cytoflow studies the effect of ganciclovir (0.05–5000 μg/mL) on TNF-a induced expression of intercellular adhesion molecule 1 (ICAM-1) in endothelial cells derived from umbilical veins (HUVEC), human coronary endothelial cells (HCAEC), and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of ganciclovir (0.05–5000 μg/mL) on cell proliferation (HUVEC, HCAEC, and HCMSMC). In part III cytotoxic effects of ganciclovir (0.05–5000 μg/mL) were studied (HUVEC, HCAEC, and HCMSMC).ResultsGanciclovir caused slight but significant inhibitory effects on expression of ICAM-1 in HUVEC, HCAEC, and HCMSMC. In all three cell types studied strong dose depending significant antiproliferative effects of ganciclovir were detected. Partially, the antiproliferative effects of ganciclovir were caused by cytotoxic effects.ConclusionsSI/MPL-ratio’s >1 in HCAEC and HCMSMC indicate that the inhibitory effects of gancliclovir on ICAM-1-expression and cell proliferation may only be expected in vivo following local high dose administration e.g. in drug eluting stents (DES).

Serum Levels of IL‐1β, IL‐6, TGF‐β, and MMP‐9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP‐9 in a New In Vitro Model of THP‐1 Cells Activated by Stenting

“…IL-1 β is a cytokine that plays a critical role in inflammatory complications after coronary stent placement, including ISR and stent thrombosis [ 10 ]. After it is released by injured cells, it stimulates endothelial cells to secrete chemokines and increases the expression of vascular adhesion molecules, which eventually leads to restenosis [ 10 , 47 , 48 ]. IL-6 works as a messenger cytokine in the expression of C-reactive protein, fibrinogen, and plasminogen activator inhibitor-1 and accelerates oxygen radical production [ 49 , 50 ].…”

Expression analysis of intercellular adhesion molecule-2 (ICAM-2) in the context of classical cardiovascular risk factors in acute coronary syndrome patients

“…Inhibited expression of ICAM-1 can also result from treating cells with ganciclovir. It cannot be excluded, though, that the antiproliferative effect can result from drug cytotoxicity [ 10 ].…”

Updated Estimates of Radiation Risk for Cancer and Cardiovascular Disease: Implications for Cardiology Practice

“…Numerous biological mechanisms have been postulated to elucidate the association between low-dose radiation and cardiovascular disease. While the primary mechanism remains incompletely understood, various processes have been suggested, including endothelial dysfunction, inflammation, genetic instability, and an augmented occurrence of chromosome aberrations in vascular smooth muscle cells and endothelial cells' DNA [15][16][17][18][19][20][21]. Additional proposed mechanisms encompass oxidative stress, modifications in coagulation and platelet activity, vascular senescence, apoptosis, and autophagy [22][23][24][25].…”