BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model

Li, De; Ma, Shuangtao; Yang, Yongjian; Yang, Dachun; Li, Gang; Zhang, Xin; Zhu, Jun; Sun, Meiqin; Tang, Bing

doi:10.3892/mmr.2011.438

Cited by 2 publications

(1 citation statement)

References 11 publications

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“…Li and colleagues [37] disclosed that the increased expression of PDGF mRNA was found on carotid artery balloon dilatation rat. Experimental results suggested that PDGF could activate its upstream pathways via directly binding PDGFR-β, which initiated intermediate signal protein, activated mitogen activated protein kinase pathway (MAPK) cascade afterwards and promoted proliferation, migration and angiogenesis in smooth muscle cells through dimerization and autophosphorylation of tyrosine residues phosphorylated [38,39].…”

Section: Resultsmentioning

confidence: 99%

Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach

et al. 2012

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BackgroundTorcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor which raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol level, has been documented to increase mortality and cardiac events associated with adverse effects. However, it is still unclear the underlying mechanisms of the off-target effects of torcetrapib.ResultsIn the present study, we developed a systems biology approach by combining a human reassembled signaling network with the publicly available microarray gene expression data to provide unique insights into the off-target adverse effects for torcetrapib. Cytoscape with three plugins including BisoGenet, NetworkAnalyzer and ClusterONE was utilized to establish a context-specific drug-gene interaction network. The DAVID functional annotation tool was applied for gene ontology (GO) analysis, while pathway enrichment analysis was clustered by ToppFun. Furthermore, potential off-targets of torcetrapib were predicted by a reverse docking approach. In general, 10503 nodes were retrieved from the integrative signaling network and 47660 inter-connected relations were obtained from the BisoGenet plugin. In addition, 388 significantly up-regulated genes were detected by Significance Analysis of Microarray (SAM) in adrenal carcinoma cells treated with torcetrapib. After constructing the human signaling network, the over-expressed microarray genes were mapped to illustrate the context-specific network. Subsequently, three conspicuous gene regulatory networks (GRNs) modules were unearthed, which contributed to the off-target effects of torcetrapib. GO analysis reflected dramatically over-represented biological processes associated with torcetrapib including activation of cell death, apoptosis and regulation of RNA metabolic process. Enriched signaling pathways uncovered that IL-2 Receptor Beta Chain in T cell Activation, Platelet-Derived Growth Factor Receptor (PDGFR) beta signaling pathway, IL2-mediated signaling events, ErbB signaling pathway and signaling events mediated by Hepatocyte Growth Factor Receptor (HGFR, c-Met) might play decisive characters in the adverse cardiovascular effects associated with torcetrapib. Finally, a reverse docking algorithm in silico between torcetrapib and transmembrane receptors was conducted to identify the potential off-targets. This screening was carried out based on the enriched signaling network analysis.ConclusionsOur study provided unique insights into the biological processes of torcetrapib-associated off-target adverse effects in a systems biology visual angle. In particular, we highlighted the importance of PDGFR, HGFR, IL-2 Receptor and ErbB1tyrosine kinase might be direct off-targets, which were highly related to the unfavorable adverse effects of torcetrapib and worthy of further experimental validation.

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Section: Resultsmentioning

confidence: 99%

Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach

et al. 2012

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Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E-deficient mice

Zheng

Wang

Zhang

et al. 2014

Molecular Medicine Reports

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The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold‑induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week‑old, apolipoprotein E (ApoE)‑deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4˚C for 4 h per day, while the mice in the control group were kept in a room at 24˚C. Cold‑exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low‑density lipoprotein and high‑density lipoprotein. The hematoxylin and eosin‑stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (P<0.01). Furthermore, cold‑treated mice exhibited significantly decreased plaque collagen and vascular smooth muscle cell deposition and increased macrophage and lymphocyte content (P<0.05 or P<0.01), which are typical features of atherosclerotic plaque instability. Additionally, the protein expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and MMP‑14 were significantly increased (P<0.05 or P<0.01), whereas tissue inhibitor of matrix metalloproteinase (TIMP)‑1 expression was decreased (P<0.05) following exposure to a cold environment. The present study demonstrated that chronic intermittent cold stress may increase atherosclerotic plaque size and promote plaque instability in ApoE‑deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments.

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BTEB2 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model

Cited by 2 publications

References 11 publications

Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach

Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach

Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E-deficient mice

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