Modulation of atherogenic lipidome by cigarette smoke in apolipoprotein E-deficient mice

Boué, Stéphanie; Tarasov, Kirill V.; Jänis, Minna T.; Lebrun, Stefan; Hurme, Reini; Schlage, Walter K.; Lietz, Michael; Vuillaume, Gregory; Ekroos, Kim; Steffen, Yvonne; Peitsch, Manuel C.; Laaksonen, Reijo; Hoeng, Julia

doi:10.1016/j.atherosclerosis.2012.09.032

Cited by 50 publications

(63 citation statements)

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“…S1P receptor is expressed by ECs and it binds its ligand S1P, a bioactive lipid with numerous functions in the immune and cardiovascular systems. Using a lipidomics approach, we have previously shown that CS exposure increases, whereas cessation decreases, the levels of S1P in plasma of ApoE -/- mice [5,22]. Furthermore, CD36 is a glycoprotein expressed in various vascular and circulatory cell types including monocytes, macrophages, platelets, ECs and adipocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Cigarette smoking has been epidemiologically established as a major risk factor for atherosclerosis and shown to promote plaque development in experimental animal models [3-5]. Mechanistically, endothelial dysfunction is thought to be a key initiating cellular event that results from a variety of pro-atherogenic stimuli including cigarette smoke (CS), dyslipidemia and oxidative stress [6-8].…”

Section: Introductionmentioning

confidence: 99%

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A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

León

Boué

Schlage

et al. 2014

Journal of Translational Medicine

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BackgroundNumerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting.MethodsWe constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis.ResultsUtilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE-/- mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques.ConclusionsWe have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

León

Boué

Schlage

et al. 2014

Journal of Translational Medicine

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“…It is a filter cigarette with reported mainstream smoke yields per cigarette of 11.0 mg total particulate matter (TPM), 0.73 mg nicotine, and 12.0 mg carbon monoxide (CO) (http://www2.ca.uky.edu/refcig/3R4F%20Preliminary%20Analysis.pdf). All cigarettes were conditioned and smoked according to International Organization for Standardization or Health Canada Intense parameters [28, 30, 31]. Mainstream CS was diluted with filtered conditioned air to a target concentration of 750 mg TPM/m 3 , unless otherwise noted (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

et al. 2015

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BackgroundMouse models are useful for studying cigarette smoke (CS)-induced chronic pulmonary pathologies such as lung emphysema. To enhance translation of large-scale omics data from mechanistic studies into pathophysiological changes, we have developed computational tools based on reverse causal reasoning (RCR).ObjectiveIn the present study we applied a systems biology approach leveraging RCR to identify molecular mechanistic explanations of pathophysiological changes associated with CS-induced lung emphysema in susceptible mice.Methods The lung transcriptomes of five mouse models (C57BL/6, ApoE−/−, A/J, CD1, and Nrf2−/−) were analyzed following 5–7 months of CS exposure.Results We predicted 39 molecular changes mostly related to inflammatory processes including known key emphysema drivers such as NF-κB and TLR4 signaling, and increased levels of TNF-α, CSF2, and several interleukins. More importantly, RCR predicted potential molecular mechanisms that are less well-established, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1, and N-COR, and reduced protein abundance of ITGB6 and CFTR. We corroborated several predictions using targeted proteomic approaches, demonstrating increased abundance of CSF2, C/EBPα, C/EBPβ, PU.1, BRCA1, and STAT1.Conclusion These systems biology-derived candidate mechanisms common to susceptible mouse models may enhance understanding of CS-induced molecular processes underlying emphysema development in mice and their relevancy for human chronic obstructive pulmonary disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00011-015-0820-2) contains supplementary material, which is available to authorized users.

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“…In mouse models exposure to mainstream cigarette smoke led to perturbations of lipid metabolism, arterial endothelial cell function and the development of atherosclerotic lesions (Boue et al, 2012). Cessation of smoke exposure led to decelerated plaque progression and decreased accumulation of pro-atherogenic lipids (Lietz et al, 2013).…”

Section: Risk Factors: Concordance Of Mouse and Human Studiesmentioning

confidence: 99%

Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

et al. 2017

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Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWAS) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWAS. In particular, of the 46 genes with strong association signals in CAD-GWAS that were studied in mouse models all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWAS with 263 from mouse studies and observed that over 50% were consistent between both species.

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Modulation of atherogenic lipidome by cigarette smoke in apolipoprotein E-deficient mice

Cited by 50 publications

References 20 publications

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

Transcriptional profiling and targeted proteomics reveals common molecular changes associated with cigarette smoke-induced lung emphysema development in five susceptible mouse strains

Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

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