Conventional therapies fail to target inflammation and immune imbalance in subjects with stable coronary artery disease: A system-based approach

Kapoor, Divya; Trikha, D.; Vijayvergiya, Rajesh; Kaul, Deepak; Dhawan, Veena

doi:10.1016/j.atherosclerosis.2014.10.009

Cited by 14 publications

(3 citation statements)

References 43 publications

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“…Some of the diverse hallmarks of endothelial activation that we observed, have previously been associated with atherosclerosis development in humans[ 49 , 58 ]. Further indications come from reports showing that OSM is present in both murine and human plaques[ 16 ], and higher mRNA expression levels of OSM in PBMCs derived from coronary artery disease patients compared to healthy individuals[ 59 ]. Moreover, a recent paper showed that prevention of OSM signaling, as opposed to stimulation of OSM signaling in our study, in OSMR-β -/- ApoE -/- mice resulted in less and smaller atherosclerotic lesions and less macrophages compared to ApoE -/- mice[ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cytokine oncostatin M induces endothelial activation in macro- and microvascular endothelial cells and in APOE*3Leiden.CETP mice

Keulen¹,

Pouwer²,

Pasterkamp³

et al. 2018

PLoS ONE

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AimsEndothelial activation is involved in many chronic inflammatory diseases, such as atherosclerosis, and is often initiated by cytokines. Oncostatin M (OSM) is a relatively unknown cytokine that has been suggested to play a role in both endothelial activation and atherosclerosis. We comprehensively investigated the effect of OSM on endothelial cell activation from different vascular beds and in APOE*3Leiden.CETP mice.Methods and resultsHuman umbilical vein endothelial cells, human aortic endothelial cells and human microvascular endothelial cells cultured in the presence of OSM express elevated MCP-1, IL-6 and ICAM-1 mRNA levels. Human umbilical vein endothelial cells and human aortic endothelial cells additionally expressed increased VCAM-1 and E-selectin mRNA levels. Moreover, ICAM-1 membrane expression is increased as well as MCP-1, IL-6 and E-selectin protein release. A marked increase was observed in STAT1 and STAT3 phosphorylation indicating that the JAK/STAT pathway is involved in OSM signaling. OSM signals through the LIF receptor alfa (LIFR) and the OSM receptor (OSMR). siRNA knockdown of the LIFR and the OSMR revealed that simultaneous knockdown is necessary to significantly reduce MCP-1 and IL-6 secretion, VCAM-1 and E-selectin shedding and STAT1 and STAT3 phosphorylation after OSM stimulation. Moreover, OSM administration to APOE*3Leiden.CETP mice enhances plasma E-selectin levels and increases ICAM-1 expression and monocyte adhesion in the aortic root area. Furthermore, Il-6 mRNA expression was elevated in the aorta of OSM treated mice.ConclusionOSM induces endothelial activation in vitro in endothelial cells from different vascular beds through activation of the JAK/STAT cascade and in vivo in APOE*3Leiden.CETP mice. Since endothelial activation is an initial step in atherosclerosis development, OSM may play a role in the initiation of atherosclerotic lesion formation.

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Section: Discussionmentioning

confidence: 99%

Inflammatory cytokine oncostatin M induces endothelial activation in macro- and microvascular endothelial cells and in APOE*3Leiden.CETP mice

Keulen¹,

Pouwer²,

Pasterkamp³

et al. 2018

PLoS ONE

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“…Pathway analysis correlated the expression to inflammation and metabolic processes and identified cancer, arthritis, and adipogenesis as relevant. A recent study identified potential target genes for therapy for inflammation ( COX-2 ), immune imbalance ( IL-8 ), and active atherosclerosis ( OSM ) [26]. These genes were all downregulated with OLE.…”

Section: Discussionmentioning

confidence: 99%

Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression

Boss

Kao

Murray

et al. 2016

IJMS

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Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted.

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“…At the molecular level, mitogen-activated protein kinase (MAPK) signaling pathways play a prominent role as modulators of stress and inflammatory responses in CVD, particularly during the atherogenesis process [5]. Inactivation of MAPKs by dual-specificity phosphatase 1 (DUSP1), also called mitogen-activated protein kinase phosphatase (MKP-1), was recently shown to be increased in circulating blood cells of CVD patients even after treatment with conventional drugs, such as statins [6]. However, the question as to whether DUSP1 influences atherogenesis and thereby CVDs is still controversial and remains to be clarified [7]; indeed, DUSP1 has been reported to be both antiatherogenic [8] and proatherogenic [9].…”

Section: Introductionmentioning

confidence: 99%

DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases

et al. 2018

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Background Cardiovascular disease (CVD) risks persist in patients despite the use of conventional treatments. This might be due to chronic inflammation as reflected in epidemiological studies associating circulating low-grade inflammatory markers with CVD recurrent events. Here, we explored this potential link by assessing plasma dual-specificity phosphatase 1 (DUSP1) levels and comparing them to high-sensitivity CRP (hsCRP) and oxidized low-density lipoprotein (oxLDL) levels and their associations to conventional CVD risk factors in confirmed CVD patients. Methods Human adults with reported CVD (n = 207) and controls (n = 70) living in Kuwait were used in this study. Anthropometric and classical biochemical parameters were determined. Plasma levels of DUSP1, oxLDL, and hsCRP were measured using human enzyme-linked immunosorbent assay kits. Results DUSP1 and hsCRP plasma levels and their least square means were higher in CVD cases, while oxLDL plasma levels were lower (p < 0.05). Multivariate logistic regression analysis showed that DUSP1 and hsCRP are independently associated with CVD in the studied population, as reflected by 2-fold and 1.5-fold increased risks with increased levels of DUSP1 and hsCRP, respectively. In our study, DUSP1 levels were found to be associated with CVD despite statin treatment and diabetes status (p < 0.05), whereas hsCRP mainly correlated with obesity markers. Conclusions Circulating DUSP1 might be a predictor of chronic subclinical inflammation and residual risk in CVD patients, whereas our data suggest that the association between hsCRP and CVD is largely accounted for adiposity risk factors.

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Conventional therapies fail to target inflammation and immune imbalance in subjects with stable coronary artery disease: A system-based approach

Cited by 14 publications

References 43 publications

Inflammatory cytokine oncostatin M induces endothelial activation in macro- and microvascular endothelial cells and in APOE*3Leiden.CETP mice

Inflammatory cytokine oncostatin M induces endothelial activation in macro- and microvascular endothelial cells and in APOE*3Leiden.CETP mice

Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression

DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases

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