Two preferentially expressed proteins protect vascular endothelial cells from an attack by peptide-specific CTL.

Vascular endothelial cells (EC) are an exposed tissue with intimate contact with circulating Ag-specific CTL. Experimental in vitro and clinical data suggested that endothelial cells present a different repertoire of MHC class I-restricted peptides compared with syngeneic leukocytes or epithelial cells. This endothelial-specific peptide repertoire might protect EC from CTL-mediated cell death.

Invariant natural killer T cells: linking inflammation and neovascularization in human atherosclerosis.

Atherosclerosis, a chronic inflammatory lipid storage disease of large arteries, is complicated by cardiovascular events usually precipitated by plaque rupture or erosion. Inflammation participates in lesion progression and plaque rupture. Identification of leukocyte populations involved in plaque destabilization is important for effective prevention of cardiovascular events.

Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation.

Background: The possibility that allogeneic hematopoietic stem cell transplantation performed across the ABO blood group-barrier is associated with an increase of graft-versus-host disease, in particular endothelial damage, has not been elucidated so far. For this reason, we investigated the level of endothelial cell chimerism after allogeneic hematopoietic stem cell transplantation in order to delineate the role of hematopoietic stem cells in endothelial replacement.

Design And Methods: The frequency of donor-derived endothelial cells was analyzed in 52 hematopoietic stem cell transplant recipients, in 22 normal skin biopsies, in 12 skin samples affected by graft-versus-host disease, various tissues from five autopsies and four secondary solid tumors by ABH immunohistochemistry, XY fluorescence in situ hybridization and short tandem repeat analysis of laser captured endothelial cells.

[Molecular tests in modern medicine - concepts, technical aspects and future direction].

Early diagnosis by molecular tests has increasingly catched attention after deciphering the complete human genome sequence in 2001. Meanwhile, complete genome sequencing will soon become available for each individual. Molecular testing is standard of care in certain infectious or malignant diseases.

A CETP polymorphism improves the diagnostic power of clinical examination in patients with cardiovascular disease.

Aims: Atherosclerosis is common and myocardial infarction, stroke and peripheral arterial occlusive disease are its devastating complications. Accurate risk prediction is urgently needed. We applied molecular tests to improve early clinical identification of patients threatened by a future course of complicated active atherosclerosis.

Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and interventional research.

Animal models facilitate our understanding of human disease by providing a controlled environment permitting testing of mechanisms of disease, diagnostic technologies and therapeutic interventions. The ideal animal model should display coronary lesions resembling those seen in human atherosclerosis. No suitable large animal model of high-risk (vulnerable) plaque exists.

Requirements for CD8 T-cell migration into the human arterial wall.

Atherosclerotic lesions develop in the arterial intima. Among the leukocytes that accumulate in advanced atherosclerotic plaques, CD8 T cells play a quantitatively important role. They may be involved in disease progression and plaque destabilization, leading to plaque rupture or erosion.

Vascular endothelium and graft-versus-host disease.

Vascular endothelial cells are an exposed target tissue for immune-mediated injury during graft-versus-host disease (GVHD). However, widespread endothelial death resulting in multi-organ failure similar to that in hyperacute solid-organ transplant rejection is not observed during GVHD. The rather mild endothelial injury seen in histological samples from affected skin biopsies contrasts with severe epithelial injury observed sometimes simultaneously.

Cutaneous graft-versus-host disease: a guide for the dermatologist.

Graft-versus-host disease (GVHD) is defined by the aggregation of clinical and pathological manifestations in a recipient of allogeneic stem cells or bone marrow transplantation in which specific immunological as well as nonspecific phenomena lead to characteristic features. GVHD is one of the major complications after hematopoietic stem cell transplantations and responsible for posttherapeutic morbidity, mortality and decrease in quality of life of those patients. GVHD is critically induced and maintained by donor immunocompetent cells that particularly attack epithelia of fast proliferating tissues such as those from the liver, gastrointestinal tract and skin.

Individual assessment of arteriosclerosis by empiric clinical profiling.

Background: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals.

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: arteritis or atherosclerosis?

A woman with a history of systemic lupus erythematosus presented with extensive bilateral strokes due to acute inflammatory, occlusive large vessel disease affecting several aortic branches including the carotid, subclavian, renal, and iliac arteries. We quantitatively characterized the arterial inflammation in this patient and compared it with the inflammatory infiltrates from 22 patients with conventional atherosclerosis. Profound histomorphologic differences from conventional atherosclerosis (predominance of CD8-positive lymphocytes, relative absence of macrophages, no ectopic neovascularization, no signs of plaque hemorrhage, concentric instead of eccentrical stenosis) suggest that this patient's accelerated arteriopathy was precipitated by pathogenic events other than conventional atherosclerosis.

Increased apolipoprotein deposits in early atherosclerotic lesions distinguish symptomatic from asymptomatic patients.

Objective: Apolipoprotein E (apoE) and apolipoprotein B100 (apoB) are both involved in receptor-mediated uptake of atherogenic lipoproteins by the liver. Inefficient hepatic clearance of these lipoproteins leads to symptomatic atherosclerosis. Using arterial tissue microarrays, we tested the hypothesis that apoE and apoB accumulation in the arterial wall discriminates between patients with symptomatic atherosclerosis and patients who never experienced cardiovascular events.

Vascular endothelial cells have impaired capacity to present immunodominant, antigenic peptides: a mechanism of cell type-specific immune escape.

Vascular endothelial cells (EC) are an exposed target tissue in the course of CTL-mediated alloimmune diseases such as graft-vs-host disease (GVHD) or solid organ transplant rejection. The outcome of an interaction between CTL and target cells is determined by the amount of Ag presented and the costimulatory signals delivered by the target cells. We compared human EC with leukocytes and epithelial cells as targets for peptide-specific, MHC class I-restricted CTL clones.

Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis.

Background: Atherosclerosis is complicated by cardiovascular events such as myocardial infarction, stroke, or peripheral arterial occlusive disease. Inflammation and pathological neovascularization are thought to precipitate plaque rupture or erosion, both causes of arterial thrombosis and cardiovascular events. We tested the hypothesis that arterial inflammation and angiogenic events are increased throughout the arterial tree in vulnerable patients, ie, in patients who suffered from cardiovascular events, compared with patients who never suffered from complications of atherosclerosis.

Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease.

Background: Vascular endothelial cells form the interface between recipient tissues and circulating alloreactive donor T cells after allogeneic stem cell transplantation. Vascular injury has been seen in patients with acute graft versus host disease (GVHD) in the skin. We aimed to see whether vascular injury mediated by cytotoxic T lymphocytes and microvessel loss arises in patients with chronic GVHD.