Novel anti-inflammatory therapies for the treatment of atherosclerosis

Khan, Razi; Spagnoli, Vincent; Tardif, Jean‐Claude; L’Allier, Philippe L.

doi:10.1016/j.atherosclerosis.2015.04.783

Cited by 117 publications

(81 citation statements)

References 180 publications

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“…22,23 There have been multiple reports linking CAD to inflammation. 29,36,37 In our study, we showed that under pathological conditions, ANRIL was significantly induced upon inflammatory factors and regulate genes expression downstream of NF-k B signaling. ANRIL appeared to be the regulatory lncRNA that links the 2 pathological processes together.…”

Section: Discussionmentioning

confidence: 62%

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

et al. 2015

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Antisense Noncoding RNA in the INK4 Locus (ANRIL) is the prime candidate gene at Chr9p21, the welldefined genetic risk locus associated with multiple human diseases including coronary artery disease (CAD), while little is known regarding its role in the pathological processes. Endothelial dysfunction triggers atherosclerotic processes that are causatively linked to CAD. To evaluate the function of ANRIL in human endothelial cells (ECs), we examined ANRIL expression under pathological stimuli and found ANRIL was markedly induced by pro-inflammatory factors. Loss-of-function and chromatin immunoprecipitation approaches revealed that NF-kB mediates TNF-a induced ANRIL expression. RNA sequencing revealed that ANRIL silencing dysregulated expression of inflammatory genes including IL6 and IL8 under TNF-a treatment. We explored the regulatory mechanism of ANRIL on IL6/8 and found that Yin Yang 1 (YY1), an ANRIL binding transcriptional factor revealed by RNA immunoprecipitation, was required for IL6/8 expression under TNF-a treatment. YY1 was enriched at promoter loci of IL6/8 and ANRIL silencing impaired the enrichment, indicating a cooperation between ANRIL and YY1 in the regulation of inflammatory genes. For the first time, we establish the connection between ANRIL and NF-kB pathway and show that ANRIL regulates inflammatory responses through binding with YY1. The newly identified TNF-a-NF-kB-ANRIL/YY1-IL6/8 pathway enhances understanding of the etiology of CAD and provides potential therapeutic target for treatment of CAD.

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Section: Discussionmentioning

confidence: 62%

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

et al. 2015

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“…MCP-1, a potent monocyte attractant, also contributes to monocyte recruitment [30]. Recently, anti-inflammatory therapies have been proposed as possible adjuncts to the current treatment for AS [31]. Zedoarondiol has been reported to have an anti-inflammatory effect on LPS-stimulated murine macrophage [6].…”

Section: Discussionmentioning

confidence: 99%

Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation

Mao

Tao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Zedoarondiol, a sesquiterpene lactone compound, showed an anti-proliferative activity on vascular smooth muscle cells in our previous study. However, whether it has a beneficial effect on endothelial cells injury induced by oxidized low-density lipoprotein (ox-LDL) remains unclear. This study was designed to investigate the protective effect of zedoarondiol on ox-LDL-induced injury of endothelial cells and explored its underlying mechanism. Methods: The protective effect of zedoarondiol on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury were evaluated by Cell Counting Kit-8 (CCK-8) assay and released lactic dehydrogenase (LDH) activity assay. Oxidative stress was determined by malonedialdehyde (MDA) content and superoxide dismutase (SOD) activity. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The culture supernatant was collected for enzyme linked immune-sorbent assays (ELISA) of interleukine-1β (IL-1β), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence staining was used to observe NF-E2-related factor 2 (Nrf2) translocation. Western blotting was performed to determine the expression of IL-1β, TNF-α, MCP-1, Kelch-like ECH associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and Nrf2. Results: Zedoarondiol attenuated HUVECs injury, up-regulated SOD activity, suppressed formation of MDA and ROS, and secretion and protein expression of IL-1β, TNF-α, and MCP-1 in injured HUVECs induced by ox-LDL. Zedoarondiol induced nuclear Nrf2 translocation from cytoplasm into nucleus and up-regulated expression of HO-1, NQO1, and Nrf2 in nucleus. All-trans-retinoic acid (ATRA), an inhibitor of Nrf2, abolished zedoarondiol-mediated anti-oxidative effect. Conclusion: Zedoarondiol attenuates ox-LDL-induced endothelial cells injury by inhibiting oxidative stress and inflammation via Nrf2/HO-1 pathway, suggesting that zedoarondiol might be meaningful on prevention and treatment of atherosclerosis.

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“…In support of this finding, it was shown that the treatment with this mAb diminished the arterial wall expression of the proinflammatory cytokines IL-1ȕ and TNFĮ. Murine models of atherosclerosis as well as clinical studies provide clear evidence that reduction of proinflammatory cytokines expression results in a limited atherosclerotic plaque development and progression [71][72][73].…”

Section: Discussionmentioning

confidence: 99%

Arresting progressive atherosclerosis by immunization with an anti-glycosaminoglycan monoclonal antibody in apolipoprotein E-deficient mice

Delgado-Roche

Brito

Acosta³

et al. 2015

Free Radical Biology and Medicine

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Novel anti-inflammatory therapies for the treatment of atherosclerosis

Cited by 117 publications

References 180 publications

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation

Arresting progressive atherosclerosis by immunization with an anti-glycosaminoglycan monoclonal antibody in apolipoprotein E-deficient mice

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