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

Background: Treatment 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.

Pulsed perfusion in a venous human organ culture model with a Windkessel function (pulsed perfusion venous HOC-model).

Background: The effectiveness of human saphenous vein grafting is limited by hyperplasia of the vessel wall. The current paper reports on a pulsed perfused venous human organ culture model (pp-venous HOC-model) with a Windkessel function.

Material/methods: Saphenous vein grafts from 21 patients undergoing coronary bypass grafting were cultured either in venous or arterial hemodynamic conditions.

Valproic acid inhibits proliferation of human coronary vascular cells (SI/MPL-ratio: 0.5): a novel candidate for systemic and local therapy of postinterventional restenosis.

Objectives: The branched-chain fatty acid, valproic acid (VPA), is the most commonly used anti-epileptic drug for treating generalized epilepsy. Recently antiproliferative effects of VPA have been described in human cancer cells, and phase I trials for the treatment of solid tumors have been initiated. In cardiologic patients, increased cell proliferation and migration from the media into the subendothelial space are the key events causing restenosis after coronary angioplasty and stenting.

Myocardial inflammation and non-ischaemic heart failure: is there a role for C-reactive protein?

Whereas C-reactive protein (CRP) is acknowledged as a cardiovascular risk marker, there is ongoing discussion about its role as a risk factor. Previous studies focused on the effects of CRP on ischaemic heart failure and atherosclerosis. In this study we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients suffering from non-ischaemic heart failure and their implication on clinical parameters.

HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia.

Background: The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.

Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratios.

Background: Sirolimus (SRL, Rapamycin) has been used successfully to inhibit restenosis both in drug eluting stents (DES) and after systemic application. The current study reports on the effects of SRL in various human in vitro/ex vivo models and evaluates the theoretical clinical relevance of the data by SI/MPL- and SI/DES-ratio's.

Methods: Definition of the SI/MPL-ratio: relation between significant inhibitory effects in vitro/ex vivo and the maximal plasma level after systemic administration in vivo (6.

Low-dose irradiation stimulates TNF-alpha-induced ICAM-1 mRNA expression in human coronary vascular cells.

Background: Low-dose irradiation (LDI) is employed to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Stimulation of adhesion molecule 1 (ICAM-1) is one of many mechanisms important in the early stages of atherosclerosis and restenosis. This study investigates the effect of gamma-irradiation on mRNA expression of ICAM-1 in human coronary vascular cells.

A perfused renal human organ culture model: impact of monocyte attack.

Background: Key processes of atherosclerosis and restenosis are triggered and/or modified by the contact of human monocytes (MCs) with the inner layers of the arterial vessel wall. This is the first report on monocyte attack in a perfused renal human organ culture model (perfused renal HOC-model).

Material/methods: Parts of the renal arteries were extracted during routine nephrectomies.

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression.

Background: Low dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC.

Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio.

Background: The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation.

Methods: ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.

Antiproliferative profile of sirolimus and mycophenolate mofetil: impact of the SI/MPL ratio.

Background: Recently, preliminary data of the ORBIT study have been presented; coronary restenosis after oral treatment with sirolimus (SRL) was merely 7.7%. The present study thought to investigate the antiproliferative profile of SRL and mycophenolate mofetil (MMF), both as individual compounds and as a combined therapy.

Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

Background: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating.

Methods And Results: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.

Effects of mycophenolate mofetil on key pattern of coronary restenosis: a cascade of in vitro and ex vivo models.

Background: Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is a rationally designed immunosuppressive drug. The current study investigates the effect of MMF on key pattern of restenosis in a cascade of in vitro and ex vivo models.

Methods: Part I of the study investigated in northern blot and cytoflow studies the effect of MMF (50, 100, 150, 200, 250, and 300 microg/mL) on TNF-alpha induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC).

Rapamycin attenuates vascular wall inflammation and progenitor cell promoters after angioplasty.

Rapamycin combines antiproliferative and antiinflammatory properties and reduces neointima formation after angioplasty in patients. Its effect on transcriptional programs governing neointima formation has not yet been investigated. Here, we systematically analyzed the effect of rapamycin on gene expression during neointima formation in a human organ culture model.

Human cytomegalovirus infection in human renal arteries in vitro.

Studies with animal cytomegaloviruses, epidemiological data from humans as well as in vitro studies suggest the involvement of the human cytomegalovirus (HCMV) in the development of atherosclerosis. Cell culture systems are insufficient for examination of the entire pathogenetic process and a satisfactory animal model for HCMV is not available. An organ culture model was established for HCMV infection of human renal arteries in vitro.

Simultaneous intra/extravascular administration of antiproliferative agents as a new strategy to inhibit restenosis: the peak of reactive cell proliferation as a hallmark for the duration of the treatment.

Background: Strictly intravascular approaches for the treatment of postangioplasty restenosis are effective in the intima and the inner parts of the media but may be insufficient to control redundant pathways in the more outer parts of the media and the adventitia. An inverse situation may occur subsequently to a strictly extravascular approach, like the recently suggested pericardial approach in pigs. We hypothesized that simultaneous intra/extravascular administration of anti-restenotic agents inhibits restenosis by blocking all stimulatory pathways in the entire arterial wall.