We have utilized a murine model of house dust mite-induced asthma to identify that an apolipoprotein E - low density lipoprotein (LDL) receptor pathway in the lung functions as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia (Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Yao X, Fredriksson K, Yu ZX, Xu X, Raghavachari N, Keeran KJ, Zywicke GJ, Kwak M, Amar MJ, Remaley AT, Levine SJ. Am J Respir Crit Care Med. 2010 Jul 9. Epub ahead of print). This identified a novel mechanism by which the pathogenesis of house dust mite-induced asthma is modulated. Ongoing experiments are utilizing mice with deletions of candidate genes in candidate apoE-LDLR signaling pathways to define further the mechanisms by which apoE-LDLR signaling negatively regulates airway hyperreactivity and goblet cell hyperplasia in asthma.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$482,980
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Yao, Xianglan; Gordon, Elizabeth M; Barochia, Amisha V et al. (2016) The A's Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma. Chest 150:283-8
Yao, Xianglan; Gordon, Elizabeth M; Figueroa, Debbie M et al. (2016) Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease. Am J Respir Cell Mol Biol 55:159-69
Mishra, Amarjit; Yao, Xianglan; Levine, Stewart J (2013) From bedside to bench to clinic trials: identifying new treatments for severe asthma. Dis Model Mech 6:877-88
Dai, Cuilian; Yao, Xianglan; Keeran, Karen J et al. (2012) Apolipoprotein A-I attenuates ovalbumin-induced neutrophilic airway inflammation via a granulocyte colony-stimulating factor-dependent mechanism. Am J Respir Cell Mol Biol 47:186-95
Vaisman, Boris L; Demosky, Stephen J; Stonik, John A et al. (2012) Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis. J Lipid Res 53:158-67
Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin et al. (2012) Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice. Am J Physiol Lung Cell Mol Physiol 302:L206-15
Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin et al. (2011) 5A, an apolipoprotein A-I mimetic peptide, attenuates the induction of house dust mite-induced asthma. J Immunol 186:576-83
Yao, Xianglan; Fredriksson, Karin; Yu, Zu-Xi et al. (2010) Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Am J Respir Crit Care Med :