Article

Atherogenic and pulmonary responses of ApoE- and LDL receptor-deficient mice to sidestream cigarette smoke

Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA.
Toxicology (Impact Factor: 3.75). 05/2012; 299(2-3):133-8. DOI: 10.1016/j.tox.2012.05.015
Source: PubMed

ABSTRACT Plasma lipoproteins play important roles in the development and progression of atherosclerosis. Two widely used mouse models of experimental atherosclerosis, apolipoprotein E-deficient (ApoE -/-) and LDL receptor-deficient (LDLr -/-) mice, have major differences in lipoprotein characteristics. These include differences in lipoprotein cholesterol distribution, lipoprotein compositions, apoliporoteins distribution, and susceptibility to oxidation. In the present study, we compared pulmonary and cardiovascular responses of ApoE -/- and LDLr -/- mice to sidestream cigarette smoke (SSCS) exposure to determine if strain differences influence their predisposition to SSCS-mediated promotion of atherosclerosis. Female ApoE -/- and LDLr -/- mice were maintained on a saturated fat enriched diet and exposed to SSCS in whole body exposure chambers for 15 weeks (4h/day, 5 days/week). At terminations, the levels of pulmonary injury markers in bronchoalveolar lavage (BAL) fluids from 6 mice per group and atherosclerotic lesion formation in 14 mice per group were analyzed. Total BAL cells and polymorphonuclear leukocytes were not significantly altered by SSCS exposure in both mouse models. Total protein, LDH, and cytokine concentrations in cell-free BAL fluids were also not significantly affected by chronic SSCS exposure in either mouse strain. SSCS significantly reduced surfactant protein D levels in both strains to a similar extent. However, SSCS exposure increased significantly the percent atherosclerotic lesion areas covering aortic intimal surfaces of ApoE -/- (control-25.3±1.52 vs. SSCS-31.9±2.02, p=0.012) as well as in LDLr -/- (control-30.97±1.1 vs. SSCS-36.61±1.7, p=0.028) mice. In contrast, the serum cholesterol concentrations of SSCS-exposed ApoE -/- mice were similar to that of controls (control-1255±85 vs. SSCS-1190±61mg/dl, p=0.552) but increased significantly in SSCS-exposed LDLr -/- mice (control-998±114 vs. SSCS-1577±142mg/dl, p=0.008). These results showing different effects of identical SSCS exposure on plasma cholesterol concentrations in these two mouse models suggest a role of multiple mechanisms in SSCS-induced atherosclerosis.

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    • "For personal use only. previous studies (Han et al., 2012). We assumed that A/J mice are appropriate for evaluating toxic responses from combined exposure of toxicants because this mouse strain is widely used in studies for tobacco-induced pulmonary toxic responses. "
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    • "However, in this study the effect on atherosclerosis was not examined. Collectively these studies in hyperlipidemic mice show that long-term CS exposure increases atherosclerotic lesion area, most likely due to effects on plasma lipid levels [3], [25], but do not provide an explanation for the link between COPD and CVD. Therefore our study contributes to the existing information by showing that emphysema per se does not affect atherosclerosis development. "
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    • "They are, however, often studied in isolation and the increased risk of cardiovascular disease in COPD patients is often underestimated (Nussbaumer-Ochsner and Rabe, 2011). It is therefore very important to study endpoints that reflect both lung disease and CVD in models exposed to cigarette smoke, as was demonstrated recently by Han et al. (2012). We have previously reported the use of ApoE −/− mice to investigate the effects of mainstream cigarette smoke (CS) on plaque development (von Holt et al., 2009). "
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