Silver nanoparticles induce premutagenic DNA oxidation that can be prevented by phytochemicals from Gentiana asclepiadea.

Among nanomaterials, silver nanoparticles (AgNPs) have the broadest and most commercial applications due to their antibacterial properties, highlighting the need for exploring their potential toxicity and underlying mechanisms of action. Our main aim was to investigate whether AgNPs exert toxicity by inducing oxidative damage to DNA in human kidney HEK 293 cells. In addition, we tested whether this damage could be counteracted by plant extracts containing phytochemicals such as swertiamarin, mangiferin and homoorientin with high antioxidant abilities.

Comparison of non-crystalline silica nanoparticles in IL-1β release from macrophages.

Background: Respirable crystalline silica (silicon dioxide; SiO₂, quartz) particles are known to induce chronic inflammation and lung disease upon long-term inhalation, whereas non-crystalline (amorphous) SiO₂ particles in the submicrometre range are regarded as less harmful. Several reports have demonstrated that crystalline, but also non-crystalline silica particles induce IL-1β release from macrophages via the NALP3-inflammasome complex (caspase-1, ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim was to study the potential of different non-crystalline SiO₂ particles from the nano- to submicro-sized range to activate IL-1β responses in LPS-primed RAW264.

The effect of agglomeration state of silver and titanium dioxide nanoparticles on cellular response of HepG2, A549 and THP-1 cells.

Nanoparticles (NPs) occurring in the environment rapidly agglomerate and form particles of larger diameters. The extent to which this abates the effects of NPs has not been clarified. The motivation of this study was to examine how the agglomeration/aggregation state of silver (20nm and 200nm) and titanium dioxide (21nm) nanoparticles may affect the kinetics of cellular binding/uptake and ability to induce cytotoxic responses in THP1, HepG2 and A549 cells.

Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells.

Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano- (20nm) and submicron- (200nm) size, and titanium dioxide nanoparticles (TiO(2)-NPs; 21nm), with emphasis on reproductive cellular- and genotoxicity.

Tumor necrosis factor superfamily molecules in acute coronary syndromes.

Accumulating evidence suggests that inflammatory pathways play an essential role in all stages of atherogenesis. Inflammatory processes are not only involved in plaque progression, but seem also to play a critical role in plaque rupture. Members of the tumor necrosis factor (TNF) superfamiliy are potent regulators of inflammation and cell survival and consist of 20 ligands that signal through 29 different receptors.

Activation of Notch signaling in cardiomyocytes during post-infarction remodeling.

Objective: Notch signaling is crucial for cell-to-cell interaction during cardiovascular development and may influence differentiation, proliferation, and apoptotic events. We investigated whether Notch signaling is activated during myocardial remodeling in heart failure (HF).

Design: Myocardial gene expression and localization of Notch receptors (Notch1-4) and ligands (Jagged1-2, and Delta-like (Dll)-1 and 4) were investigated in rats with HF after induction of myocardial infarction and in humans with HF.

Treatment with the PPARgamma agonist rosiglitazone downregulates interleukin-1 receptor antagonist in individuals with metabolic syndrome.

Objectives: Thiazolidinediones (TZDs) reduce insulin resistance, but also have pleiotropic properties including effects on inflammation. The balance between protective and proatherogenic effects may differ in various patient populations. We studied the effect of rosiglitazone on inflammatory markers in patients with metabolic syndrome (MetSyn).

The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis.

Activated platelets release a wide range of inflammatory mediators, including members of the tumour necrosis factor (TNF) superfamily (e.g. CD40 ligand [CD40L] and LIGHT).

Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis.

Objective: Based on the emerging importance of the wingless (Wnt) pathways in inflammation and vascular biology, we hypothesized a role for Dickkopf-1 (DKK-1), a major modulator of Wnt signaling, in atherogenesis and plaque destabilization.

Methods And Results: We report increased levels of DKK-1 in experimental (ApoE(-/-) mice) and clinical (patients with coronary artery disease [n=80] and patients with carotid plaque [n=47]) atherosclerosis, both systemically (serum) and within the lesion, with particularly high levels in advanced and unstable disease. We identified platelets as an important cellular source of DKK-1 as shown by in vitro experiments and by immunostaining of thrombus material obtained at the site of plaque rupture in patients with acute ST-elevation myocardial infarction, with strong immunoreactivity in platelet aggregates.

Inflammatory interaction between LIGHT and proteinase-activated receptor-2 in endothelial cells: potential role in atherogenesis.

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells.

The complex role of T-cell-based immunity in atherosclerosis.

Although the pathogenic role of T cells in atherogenesis is well established, the function of the various T-cell subsets is far from clear. Whereas activation of the T-helper type 1 (Th1) subset promotes inflammatory and proatherogenic responses and activation of Th2 cells mediates both proatherogenic and antiatherogenic effects, the newly discovered regulatory T-cell subset seems to attenuate atherogenesis. However, the dynamics of T-cell response within the plaque are still poorly understood, and both antigen-dependent and antigen-independent stimuli may be involved in the expansion of T cells in atherosclerotic plaques.

Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure.

Background: Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses.

Aims: We sought to investigate a potential pathogenic role of LIGHT in chronic HF.

High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins.

Aims: CXC ligand 16 (CXCL16) may be involved in inflammation and lipid metabolism, and we hypothesized a role for this chemokine in coronary artery disease (CAD).

Methods And Results: We performed clinical studies in CAD patients as well as experimental studies in cells with relevance to atherogenesis [i.e.

A potential role of the CXC chemokine GROalpha in atherosclerosis and plaque destabilization: downregulatory effects of statins.

Objective: We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis.

Methods And Results: GROalpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROalpha was examined in endothelial cells and THP-1 macrophages.

Raised LIGHT levels in pulmonary arterial hypertension: potential role in thrombus formation.

Rationale: Thrombus formation and inflammation are involved in the pathogenesis of pulmonary arterial hypertension (PAH), and LIGHT (Lymphotoxin-like Inducible protein that competes with Glycoprotein D for Herpesvirus entry mediator on T lymphocytes) has been shown to promote vascular inflammation.

Objectives: We sought to investigate the role of the tumor necrosis factor superfamily ligand LIGHT in the pathogenesis of PAH.

Methods: We studied 73 patients with severe PAH and 10 control subjects.

Enhanced expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental atherosclerosis: possible pathogenic role in plaque destabilization.

Objective: Based on their role in T-cell homing into nonlymphoid tissue, we examined the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in coronary artery disease (CAD).

Methods And Results: We performed studies in patients with stable (n=40) and unstable (n=40) angina and healthy controls (n=20), in vitro studies in T-cells and macrophages, and studies in apolipoprotein-E-deficient (ApoE-/-) mice and human atherosclerotic carotid plaques. We found increased levels of CCL19 and CCL21 within the atherosclerotic lesions of the ApoE-/- mice, in human atherosclerotic carotid plaques, and in plasma of CAD patients.

Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation.

Objectives: We sought to investigate the role of the CXC chemokine neutrophil-activating peptide-2 (NAP-2) in atherogenesis and plaque destabilization.

Background: Chemokines are involved in atherogenesis, but the role of NAP-2 in atherosclerotic disorders is unclear. Based on its potential pro-atherogenic properties, we hypothesized a pathogenic role for NAP-2 in coronary artery disease.

Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible role in plaque destabilization.

Objective: Based on its role in inflammation and matrix degradation, we hypothesized a role for osteoprotegerin (OPG), RANK, and RANK ligand (RANKL) in coronary artery disease.

Methods And Results: We examined the expression of various members of the OPG/RANKL/RANK axis in patients with stable and unstable angina and in the atherosclerotic lesions of apolipoprotein E-deficient (apoE(-/-)) mice. Our findings were: (1) Serum levels of OPG were raised in patients with unstable angina (n=40), but not in those with stable angina (n=40), comparing controls (n=20); (2) mRNA levels of RANKL were increased in T-cells in unstable angina patients accompanied by increased expression of RANK in monocytes; (3) strong immunostaining of OPG/RANKL/RANK was seen within thrombus material obtained at the site of plaque rupture during acute myocardial infarction; (4) OPG/RANKL/RANK was expressed in the atherosclerotic plaques of apoE(-/-) mice, with RANKL located specifically to the plaques; and (5) RANKL enhanced the release of monocyte chemoattractant peptide-1 in mononuclear cells from unstable angina patients, and promoted matrix metalloproteinase (MMP) activity in vascular smooth muscle cells.

Chemokines in children with heterozygous familiar hypercholesterolemia: selective upregulation of RANTES.

Objective: Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia.

Methods And Results: We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs) from clinically healthy children with and without heterozygous familial hypercholesterolemia (FH).

Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy.

Objective: Recent data derived primarily from studies in animal models suggest that fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis. We, therefore, hypothesized that enhanced CX3CL1/CX3CR1 expression may promote atherogenesis in patients with coronary artery disease (CAD).

Methods And Results: We examined the plasma levels of CX3CL1 and CX3CR1 expression in peripheral blood mononuclear cells (PBMC) in various CAD populations (30 patients with previous myocardial infarction, 40 patients with stable angina, 40 patients with unstable angina, and a total of 35 controls) and used various experimental approaches to characterize CX3CL1-mediated leukocyte responses.

Potential role for immunomodulatory therapy in atherosclerotic plaque stabilisation.

Our understanding of the mechanisms underlying acute coronary syndromes has evolved beyond the view that this syndrome reflects a progressive collection of lipids and cellular debris in the vascular wall. Current evidence has implicated a role for inflammation in the pathogenesis of this process. Thus, inflammatory cytokines may attenuate interstitial collagen synthesis, increase matrix degradation and promote apoptosis in several atheroma-associated cell types, and all these cellular events may enhance plaque vulnerability.