Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized.
The American Journal of Tropical Medicine and Hygiene
Single doses (250, 500, 1,000, or 2,000 units/kg) of an ovine polyclonal-specific Fab fragment directed against tumor necrosis factor-alpha (TNF-alpha) were given to 17 adult patients with severe falciparum malaria immediately before treatment with artesunate in a pilot study to assess safety and optimal dosage with a view to future studies. Clinical and laboratory variables were compared with 11 controls. In the groups given Fab, there was a tendency for a faster resolution of clinical manifestations and reduction of fever but also a tendency towards longer parasite clearance times.
Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-IRBC) in postcapillary brain endothelium is a hallmark of cerebral malaria (CM) pathogenesis. There is a correlation between adherent Pf-IRBC and increased expression of intercellular cell adhesion molecule 1 (ICAM-1), which is also a receptor for Pf-IRBC on human brain microvascular endothelial cells (HBMEC). The underlying mechanism for the increased ICAM-1 expression has not been clearly defined. Therefore, we investigated the mechanisms of ICAM-1 expression on isolated HBMEC after exposure to Pf-IRBC.
The host immune response contributes to the onset and progression of severe malaria syndromes, such as cerebral malaria. Adjunctive immunomodulatory strategies for severe malaria may improve clinical outcome beyond that achievable with artemisinin-based therapy alone. Here, we report that prophylaxis with inhaled nitric oxide significantly reduced systemic inflammation (lower TNF, IFN? and MCP-1 in peripheral blood) and endothelial activation (decreased sICAM-1 and vWF, and increased angiopoeitin-1 levels in peripheral blood) in an experimental cerebral malaria model.
BACKGROUND: Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects.
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVE: In addition to being a cardiovascular risk marker, recent studies support a role for CRP in atherothrombosis. Several investigators have reported that CRP binds to Fcgamma receptors on leukocytes. The aim of the study is to determine the processing of CRP by human aortic endothelial cells (HAECs). METHODS AND RESULTS: Binding studies were performed by incubation of HAECs with biotinylated CRP (B-CRP, 25 to 200 microg/mL) for 30 to 180 minutes at 4 degrees C. B-CRP binding was quantitated using streptavidin-fluorescein isothiocyanate followed by flow cytometry.
American Journal of Physiology. Heart and Circulatory Physiology
Monocyte-endothelial cell adhesion is a key early event in atherogenesis. C-reactive protein (CRP), a cardiovascular risk marker, is known to stimulate ICAM and VCAM in human aortic endothelial cells (HAEC) and induces monocyte-endothelial cell adhesion. In this study, we examined the mechanisms by which native CRP promotes monocyte-endothelial cell adhesion under static conditions and tested the effect of CRP on adhesion under shear flow.
Glycosylation of proteins plays multiple roles in cell-cell and cell-matrix interactions. Fucose is a monosaccharide associated with glycosylation events and is known to be over-expressed in many malignant tumors. By using alpha-L-fucosidase (alpha-L-fase), a glycosidase that specifically removes alpha-L-fucose (alpha-L-f), we have examined the potential effects of defucosylation on tumor functions, focusing on tumor progression in the context of the interaction of tumor cells with the extracellular microenvironment.
The blood-brain barrier (BBB) is dramatically but transiently compromised in the cerebella of myelin basic protein immunized mice at least 1 week prior to the development of the paralytic phase of experimental allergic encephalomyelitis (EAE). Treatment of mice with the peroxynitrite-dependent radical scavenger uric acid (UA) during the first week after immunization blocks the early increase in cerebellar BBB permeability and the subsequent development of clinical signs of EAE.
Reactive oxygen species (ROS) and oxidative stress are thought to play a central role in the etiology of cell dysfunction and tissue damage in sepsis. However, there is limited and controversial evidence from in vivo studies that ROS mediate cell signaling processes that elicit acute inflammatory responses during sepsis. Because NADPH oxidase is one of the main cellular sources of ROS, we investigated the role of this enzyme in lipopolysaccharide (LPS)-induced acute inflammation in vivo, utilizing mice deficient in the gp91(phox) or p47(phox) subunits of NADPH oxidase.