ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Metabolic Syndrome-Associated Pulmonary Lipid and Iron Accumulation and Alterations in TLR4/NF-κB Signaling and Ferroptosis-Regulatory Proteins Are Attenuated by Resveratrol Plus Quercetin in Rats.Current issues in molecular biology · 2026Article
- Ceramides and neuroinflammation as immunometabolic drivers and biomarkers of major depressive disorder, treatment-resistant depression, and suicidal vulnerability.Frontiers in pharmacology · 2026Review
- Linking Lipid Metabolism and Immune Function: New Insights into Chronic Respiratory Diseases.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Mechanism underlying the therapeutic effects of effective component compatibility of Bufei Yishen formula III combined with exercise rehabilitation on chronic obstructive pulmonary disease.Annals of medicine · 2024Article
- Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD.JCI insight · 2023Article
- The Role of Phytochemicals and Gut Microbiome in Atherosclerosis in Preclinical Mouse Models.Nutrients · 2023Review
- MicroRNA Control Lipid-laden Alveolar Macrophages in Smokers: A Potential Therapeutic Target for Chronic Obstructive Pulmonary Disease?American journal of respiratory cell and molecular biology · 2022Article
- Article
- Models Contribution to the Understanding of Sarcoidosis Pathogenesis: "Are There Good Models of Sarcoidosis?"Journal of clinical medicine · 2020Review
- Nicotine in Senescence and Atherosclerosis.Cells · 2020Review
- Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies.Pharmacology & therapeutics · 2019Review
- A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.PloS one · 2018Article
- A New Frontier in Immunometabolism. Cholesterol in Lung Health and Disease.Annals of the American Thoracic Society · 2017Review
- Parenchymal Airspace Profiling: Sensitive Quantification and Characterization of Lung Structure Evaluating Parenchymal Destruction.American journal of respiratory cell and molecular biology · 2016Article
- Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease.American journal of respiratory cell and molecular biology · 2016Review
- Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.International journal of molecular sciences · 2016Review
- The Apoe(-/-) mouse model: a suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction.Journal of translational medicine · 2016Review
- Autophagy and Obesity-Related Lung Disease.American journal of respiratory cell and molecular biology · 2016Review
- Immune Modulation of the T Cell Response in Asthma through Wnt10b.American journal of respiratory cell and molecular biology · 2016Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe(-/-)) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe(-/-) mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe(-/-) mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe(-/-) macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe(-/-) mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.
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