title: Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease.
abstract: Emerging roles are being recognized increasingly for apolipoproteins in the pathogenesis and treatment of lung diseases on the basis of their ability to suppress inflammation, oxidative stress, and tissue remodeling, and to promote adaptive immunity and host defense. Apolipoproteins, such as apolipoprotein E (apoE) and apolipoprotein A-I (apoA-I), are important components of lipoprotein particles that facilitate the transport of cholesterol, triglycerides, and phospholipids between plasma and cells. ApoE-containing lipoprotein particles are internalized into cells by low-density lipoprotein receptors (LDLRs), whereas apoA-I can interact with the ATP-binding cassette subfamily A member 1 (ABCA1) transporter to efflux cholesterol and phospholipids out of cells. ApoE and apoA-I also mediate receptor-independent effects, such as binding to and neutralizing LPS. Both apoE and apoA-I are expressed by lung cells, which allows apoE/LDLR- and apoA-I/ABCA1-dependent pathways to modulate normal lung health and the pathogenesis of respiratory diseases, including asthma, acute lung injury, cancer, emphysema, pulmonary fibrosis, and pulmonary hypertension. Data from human studies and research using experimental murine model systems have shown that both apoE and apoA-I pathways play primarily protective roles in lung biology and respiratory disease. Furthermore, apolipoprotein mimetic peptides, corresponding to the LDLR-binding domain of apoE or the class A amphipathic α-helical structure of apoA-I, have antiinflammatory and antioxidant effects that attenuate the severity of lung disease in murine models. Thus, the development of inhaled apolipoprotein mimetic peptides as a novel treatment paradigm could represent a significant advance for patients with respiratory disease who do not respond to current therapies.
authors.affiliation: Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gordon
authors.affiliation: Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Debbie M
authors.initials: DM
authors.lastname: Figueroa
authors.affiliation: Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Amisha V
authors.initials: AV
authors.lastname: Barochia
authors.affiliation: Laboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Levine
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E
keywords: apolipoprotein A-I; apolipoprotein E; lipid transport; lung disease