Endothelial dysfunction is a key triggering event in atherosclerosis. Following the entry of lipoproteins into vessel wall, their rapid modification results generation advanced glycation endproduct epitopes and subsequent infiltration inflammatory cells. These cells release receptor for (RAGE) ligands, specifically S100/calgranulins high-mobility group box 1, which sustain vascular injury. Here, we demonstrate critical roles RAGE its ligands inflammation, endothelial dysfunction,...

Abstract PD-1, a member of the CD28 family immune regulatory molecules, is expressed on activated T cells, interacts with its ligands, PD-L1/B7-H1 and PD-L2/B7-DC, other delivers inhibitory signals to cell. We studied role this pathway in modulating autoreactive cell responses two models myocarditis. In CD8+ cell-mediated adoptive transfer model, we found that compared Pd1+/+ Pd1−/− cells cause enhanced disease, increased inflammatory infiltrate, particularly rich neutrophils. Additionally,...

Leukotriene B 4 (LTB ), a potent leukocyte chemoattractant derived from the 5-lipoxygenase metabolism of arachidonic acid, exerts its action by means specific cell surface receptors, denoted BLT 1 and 2 . In this study, receptor proteins were detected in human carotid artery atherosclerotic plaques, colocalizing with markers for macrophages, endothelial cells, vascular smooth muscle cells (SMC). Challenge coronary SMC either LTB or U75302, partial agonist that is selective receptor, induced...

Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We studied contribution PD-1 pathway to regulation T cells promote atherosclerotic lesion formation inflammation.We show compared Ldlr-/- control mice, Pd1-/-Ldlr-/- mice developed larger lesions more abundant CD4+ CD8+ macrophages, accompanied by higher levels serum tumor necrosis factor-α. Iliac lymph node from proliferated αCD3 or oxidized...

Regulatory T cells (Treg) are present in atherosclerotic lesions and can modulate disease. In this study we characterized changes Treg responses associated with prolonged hypercholesterolemia lesion progression.Low-density lipoprotein receptor null mice which express green fluorescent protein were fed a control or cholesterol-rich diet, protein-positive enumerated lymphoid tissues aorta. Splenic numbers increased after 4, 8, 20 weeks cholesterol-diet-fed mice. However, the number of...

The transcription factor Krüppel-like 2 (KLF2) is required for the quiescent and migratory properties of naive T cells. Statins, a class HMG-CoA reductase inhibitors, display pleiotropic immunomodulatory effects that are independent their lipid-lowering capacity may be beneficial as therapeutic agents cell-mediated inflammatory diseases. Statins upregulate KLF2 expression in endothelial cells, this activity associated with an antiinflammatory phenotype. We therefore hypothesized statins due,...

Rationale : The multiligand RAGE (receptor for advanced glycation end products) contributes to atherosclerosis in apolipoprotein (Apo)E-null mice. Objective To delineate the specific mechanisms by which accelerated atherosclerosis, we performed Affymetrix gene expression arrays on aortas of nondiabetic and diabetic ApoE-null mice expressing or devoid at nine weeks age, as this reflected a time point frank atherosclerotic lesions were not yet present, but that would be able identify genes...

Abstract The ability of regulatory T cells (Treg) to traffic sites inflammation supports their role in controlling immune responses. This feature the idea that adoptive transfer vitro expanded human Treg could be used for treatment immune/inflammatory diseases. However, migratory behavior Treg, as well direct influence at site inflammation, remains poorly understood. To explore possibility may have anti-inflammatory influences on tissues, independent well-established suppressive effects...

T cell subset-specific migration to inflammatory sites is tightly regulated and involves interaction of the cells with endothelium. Th17 often appear at different than Th1 cells, or both subsets same but times. Differences in subset adhesion endothelium may contribute migratory behavior, this possibility has not been well studied. We examined mouse endothelial molecules under flow vitro microvessels vivo we characterized their phenotype by cytometry quantitative RT-PCR. More interacted...

Nuclear factor-kappaB (NF-kappaB)-mediated vascular inflammation is a prominent characteristic of atherogenesis and restenosis. We noted that angioplastic injury to carotid artery elicited two phases NF-kappaB activation characterized by an early in the arterial media late coupled with high levels inhibitor IkappaB kinase (IKK) activity intima. These findings prompted us elucidate role for different IKK progress repair. Our results show blockade perivascular administration pyrrolidine...

Abstract — Intimal proliferation of smooth muscle cells (SMCs) is a key event in the vascular response to injury, including early stages atherosclerosis and restenosis after angioplasty. Tumor necrosis factor-α (TNF-α) has been reported stimulate growth cultured human SMCs, but activation TNF receptors also known induce cell death by apoptosis. We report here that SMCs isolated from neointima injured rat aortas are characterized increased expression TNF-α interleukin-1β γ-interferon compared...

To gain insights into mechanisms by which intimal hyperplasia interferes with the repair process investigating expression and function of catalytic telomerase reverse transcriptase (TERT) subunit after vascular injury.Functional is essential to replicative longevity cells. We found that TERT was de novo activated in intima injured arteries, involving activation nuclear factor κB pathway. Stimulation isolated smooth muscle cell (SMC) basic fibroblast growth or tumor necrosis α resulted...

Abstract Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies shown an anti-inflammatory role for transcription factor Krüppel-like 2 (KLF2) regulating activation various cell types that participate atherosclerotic lesion development, endothelial cells,...

Although demand for information about the effectiveness and efficiency of health care technology grows, large-scale resource-intensive randomized controlled trials remain impractical. New methods are needed to translate more commonly available clinical process measures into potential impact on outcomes.The authors propose a method building mathematical models based published evidence that provides an bridge between changes resulting outcomes. This combines tools from systematic review,...

T cell subset-specific migration to inflammatory sites is tightly regulated and involves interaction of the cells with endothelium. Th17 often appear at different than Th1 cells, or both subsets same but times. Differences in subset adhesion endothelium may contribute migratory behavior, this possibility has not been well studied. We examined mouse endothelial molecules under flow vitro microvessels vivo we characterized their phenotype by cytometry quantitative RT-PCR. More interacted...

Abstract The statins, a class of HMG CoA-reductase inhibitors display immunomodulatory properties, independent their cholesterol-lowering effects. We recently demonstrated that statins modulate T cell function through upregulation the transcription factor, kruppel-like factor 2 (KLF2). Dendritic cells are essential for initiating and regulating responses. therefore examined how might DC function. found that: 1) upregulate Klf2 gene expression in both splenic bone marrow derived mouse DCs; 2)...

Regulatory T cells (Treg) can suppress proatherogenic cell responses, similar to their established function in regulating autoreactive immune-mediated/inflammatory disease. We have shown that hypercholesterolemia induces an accumulation of Treg atherosclerotic aorta, but the content is not maintained over time under sustained hypercholesterolemic conditions. Significantly, effector (Teff) aorta increased while went down concomitant with increase lesion size this period. Previous studies...

Introduction: Interleukin 17 (IL-17) is the signature cytokine produced by TH17 cells, a novel subset of pro-inflammatory CD4+ T cells. Prior studies have noted elevated serum IL-17 in patients presenting with acute coronary syndrome but little known regarding effect on endothelial (EC) activation, key step thrombosis and process leukocyte platelet recruitment to sites inflammation. Methods results: We tested hypothesis that would induce distinct pattern EC activation when compared TH1 IFNγ....

Kruppel-Like Factor 2 (KLF2) is a zinc -finger transcription factor, essential for maintenance of T cell quiescence and migration. Statins upregulate KLF2 expression in endothelial cells, but direct effects statins on cells are not characterized. We hypothesized that immunomodu-latory related partially to their influence expression. Therefore, we characterized pattern during different phases activation, examined the determined if modulated pathologic responses KLF2-dependent manner....

T cell subset specific migration to inflammatory sites is tightly regulated involving interaction of the cells with endothelium. helper 17 (Th17) often appear at same inflammation than 1 (Th1) but not simultaneously, sometimes they different and co‐existence does occur. However, Th17 adhesion vascular endothelium into tissues organs has been well studied. We examined mouse endothelial molecules under flow in vitro microvessels vivo, characterized their migratory phenotype by cytometry...