Antiinflammatory cytokines and atherosclerosis

In the 20th century, research focused on cholesterol and lipoproteins as the key mechanism in establishing atherosclerotic cardiovascular disease (ASCVD). Given that some studies demonstrated subclinical atherosclerosis in subjects without conventional cardiovascular risk factors, the elevated low-density lipoprotein (LDL) levels alone cannot account for the entire burden of atherosclerosis. Hence, large-scale clinical trials demonstrated the operation of immune and inflammatory pathways in ASCVD. In this regard, the evidence establishes that cells of the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis...

Changes in Ca2+ influx during proinflammatory stimulation modulates cellular responses, including the subsequent activation of inflammation. Whereas the involvement of Ca2+ has been widely acknowledged, little is known about the role of Na+ . Ranolazine, a piperazine derivative and established antianginal drug, is known to reduce intracellular Na+ as well as Ca2+ levels. In stable coronary artery disease patients ( n = 51) we observed reduced levels of high-sensitive C-reactive protein (CRP) 3 mo after the start of ranolazine treatment ( n = 25) as compared to the control group...

Cardiovascular disease caused by atherosclerosis is a leading cause of morbidity and mortality worldwide. Owing to the synergistic regulation of cholesterol metabolism and lesion inflammation, the simultaneous administration of statins and nucleic acids is expected to alleviate atherosclerosis. In this work, we prepared atorvastatin- and galactose-modified trimethyl chitosan nanoparticles (GTANPs) with dual targeting to hepatocytes and lesional macrophages for encapsulating Baf60a siRNA (siBaf60a) and anti-miR-33 pDNA (pAnti-miR-33), attaining the effective codelivery of statins and nucleic acids...

Atherosclerosis is considered a chronic, inflammatory disease responsible for more than 15% of all global deaths, secondary to its complications of myocardial infarction, vascular disease, and stroke. Current treatment regimens consist of lipid-lowering pharmaceuticals, control of risk factors, and prevention of plaque rupture and thrombosis with anti-platelet agents. However, a significant burden on society remains due to the morbidity and mortality of coronary artery disease (CAD) despite our best practices...

Bats have emerged as unique mammalian vectors harboring a diverse range of highly lethal zoonotic viruses with minimal clinical disease. Despite having sustained complete genomic loss of AIM2, regulation of the downstream inflammasome response in bats is unknown. AIM2 sensing of cytoplasmic DNA triggers ASC aggregation and recruits caspase-1, the central inflammasome effector enzyme, triggering cleavage of cytokines such as IL-1β and inducing GSDMD-mediated pyroptotic cell death. Restoration of AIM2 in bat cells led to intact ASC speck formation, but intriguingly resulted in a lack of caspase-1 or consequent IL-1β activation...

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls...

Accumulating observations in humans and animals indicate that inflammation plays a key role in atherosclerosis development and subsequent complications. Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and IL-18, and the atheroprotective effect of anti-inflammatory cytokines, including IL-10 and TGF-β...

PURPOSE: Colchicine is a widely available, inexpensive drug with a range of antiinflammatory properties that may make it suitable for the secondary prevention of atherosclerosis. This review examines how past and contemporary approaches to antiinflammatory therapy for atherosclerosis have led to a better understanding of the nature of the disease and sets out the reasons why colchicine has the potential to become a cornerstone therapy in its management. METHODS: We performed a literature search using PubMed, the Cochrane library, and clinical trial registries to identify completed and ongoing clinical studies on colchicine in coronary artery disease, and a PubMed search to identify publications on the mechanism of action of colchicine relevant to atherosclerosis...

The present study aimed to investigate the effect and possible mechanism of action of crocetin on the high cholesterol diet (HCD) induced atherosclerosis rat. The Wistar rats were used in the current investigation. The rats were divided into following group, Group I: control, Group II: HCD induced AS, Group III: AS + crocetin (25 mg/kg), Group IV: AS + crocetin (50 mg/kg) and Group V: AS + Simvastatin, respectively. AS was induced in the rats using the vitamin D3 and HCD. The rats received the pre-determined treatment for the 10 weeks...

Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloid-specific Csn5 deletion...

OBJECTIVES: Kefir is obtained by the action of acidic bacteria and yeasts that exist in symbiotic association in kefir grains. Recently, this fermented milk drink has been recommended for the treatment of several clinical conditions, such as inflammatory, gastrointestinal, or cardiovascular-related diseases, or a combination of these diseases. However, its effects on atherosclerosis are not yet clear. The aim of this study was to prove that chronic treatment with a soluble, nonbacterial fraction of kefir could reduce the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice...

Autoimmune-inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) have been associated with autoimmune atherosclerosis leading to increased cardiovascular risk. Traditional risk factors, genetics, as well as the role of systemic inflammation including inflammatory cells, cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. Cardiovascular risk may be determined by the use of currently available tools...

The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC)...

Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood-brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis...

AIM: Ghrelin, a gastric peptide, is involved in several metabolic and cardiovascular processes. Emerging evidence indicates the potential involvement of ghrelin in low-grade inflammatory diseases such as atherosclerosis and hypertension. Cytokine-induced inflammation is critical in these pathological states. The growth hormone secretagogue receptor (GHSR) has been identified in blood vessels, so we predict that ghrelin might inhibit proinflammatory responses in human umbilical vein endothelial cells (HUVECs)...

Sedentary lifestyle leads to the accumulation of visceral fat. This is accompanied by the infiltration of immune cells with pro-inflammatory characteristics in adipose tissue, causing an increased release of cytokines and generating a low-grade inflammatory state. It has been associated with the development of insulin resistance, atherosclerosis, neurodegeneration, and development of tumors. Exercise can be used as a treatment to improve symptoms of many of these conditions because it promotes an anti-inflammatory effect...

S100A8, S100A9 and S100A12 are considered proinflammatory mediators of atherosclerosis. Known as calgranulins, they are major components of neutrophils and are upregulated in macrophages and foam cells. They influence leukocyte recruitment, and may propagate inflammation by binding TLR4 and/or receptor for advanced glycation endproducts (RAGE). However, the receptors for calgranulins remain an enigma; we have no evidence for TLR4 or RAGE activation by S100A8 or S100A12. Moreover, gene regulation studies suggest antiinflammatory functions for S100A8 and emerging reports indicate pleiotropic roles...

The purpose of this study was to elucidate the role of nucleotide binding oligomerization domain-containing protein 2 (NOD2) signaling in atherosclerosis and periodontal bone loss using an Apolipoprotein E(-/-) (ApoE(-/-)) mouse model based on the proposed role of NOD2 in inflammation. NOD2(-/-)ApoE(-/-) and ApoE(-/-) mice fed a standard chow diet were given an oral gavage of Porphyromonas gingivalis for 15 wk. NOD2(-/-)ApoE(-/-) mice exhibited significant increases in inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and the heart compared with ApoE(-/-) mice...

Oxidized low-density lipoprotein (ox-LDL) is an important risk factor in the development of atherosclerosis. LOX-1, a lectin-like receptor for ox-LDL, is present primarily on endothelial cells and upregulated by ox-LDL, tumor necrosis factor a, shear stress, and cytokines in atherosclerosis. Recent studies demonstrated that ginkgolide B, a platelet-activating factor receptor antagonist, has antiinflammatory and antioxidant effects on endothelial and nerve cells. The present study investigated the effects of ginkgolide B on LOX-1 expression and the possible mechanism of action...

Familial hypercholesterolemia is a genetic disorder that leads to severe atherosclerosis related cardiovascular complications in young adults. Extracorporeal elimination is a method of LDL-lowering procedures effective in patients with homozygous or severe heterozygous FH utilized in cases. The recruitment of leucocytes into the arterial intima is dependent on a cascade of events mediated through a diverse family of adhesion molecules. Several pro-inflammatory adhesion molecules are cleared by various lipid apheresis methods...