Progression of atherosclerosis in the Apo E−/− model: 12-Month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet

Holt, Klaus von; Lebrun, Stefan; Stinn, Walter; Conroy, Lynda L.; Wallerath, Thomas; Schleef, Raymond R.

doi:10.1016/j.atherosclerosis.2008.11.031

Cited by 38 publications

(34 citation statements)

References 30 publications

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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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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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“…Similarly, in animal models, developmental cigarette smoke exposure (CSE) induces cardiovascular disease, hypertension, and a predisposition to obesity with a high fat diet challenge [30–33]. The putative link between developmental CSE and adult onset hypertension and cardiovascular disease may be attributed in part to a mild structural dysmorphology and proportionally smaller kidney size, which when coupled to obesity results in nephron hyperfiltration [34–37].…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that underlying metabolic dysfunction contributes to the propensity for adult onset disease in offspring developmentally exposed to cigarette smoke [30, 33, 40–43]. In our prior study of the impact of developmental CSE on kidney proteome profiles at weaning in a murine model of 'active' exposure that spanned gestation day 1 through postnatal day 21, we identified several metabolic pathways including glucose metabolism that were altered at a time point immediately after the cessation of exposure [41].…”

Section: Introductionmentioning

confidence: 99%

Developmental cigarette smoke exposure II: Kidney proteome profile alterations in 6 month old adult offspring

Neal

Jagadapillai

Chen

et al. 2016

Reproductive Toxicology

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Cigarette smoke exposure (CSE) during gestation and early development suppresses the growth trajectory in offspring. In prior studies utilizing a mouse model of ‘active’ developmental CSE (GD1-PD21), low birth weight induced by CSE persisted throughout the neonatal period and was present at the cessation of exposure at weaning with proportionally smaller kidney mass that was accompanied by impairment of carbohydrate metabolism. In the present study, littermates of those characterized in the prior study were maintained until 6 months of age at which time the impact of developmental CSE on the abundance of proteins associated with cellular metabolism in the kidney was examined. Kidney protein abundances were examined by 2D-SDS-PAGE based proteome profiling with statistical analysis by Partial Least Squares-Discriminant Analysis. Key findings of this study include a persistence of impact of developmental CSE past the original exposure period on the nucleic acid and carbohydrate metabolism networks and oxidant scavenging pathways.

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“…Atherosclerosis is the main underlying cause of CVD [2], and dyslipidemia and systemic inflammation are considered to be the most important contributors to atherosclerosis development. This increased risk of COPD patients for CVD is thus independent of common risk factors, such as smoking, which can have substantial effects on atherosclerosis development by itself [3], [4]. Current therapy of COPD patients with CVD is based on lipid-lowering treatment which is added to COPD treatment with bronchodilators and anti-inflammatory drugs [5].…”

Section: Introductionmentioning

confidence: 99%

The Effect of PPE-Induced Emphysema and Chronic LPS-Induced Pulmonary Inflammation on Atherosclerosis Development in APOE*3-LEIDEN Mice

et al. 2013

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BackgroundChronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE).MethodsHyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed.ResultsIntratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE.ConclusionThis study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.

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Progression of atherosclerosis in the Apo E−/− model: 12-Month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet

Cited by 38 publications

References 30 publications

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

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

Developmental cigarette smoke exposure II: Kidney proteome profile alterations in 6 month old adult offspring

The Effect of PPE-Induced Emphysema and Chronic LPS-Induced Pulmonary Inflammation on Atherosclerosis Development in APOE*3-LEIDEN Mice

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