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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | - |
dc.contributor.author | DRAGER, Luciano F. | - |
dc.contributor.author | YAO, Qiaoling | - |
dc.contributor.author | HERNANDEZ, Karen L. | - |
dc.contributor.author | SHIN, Mi-Kyung | - |
dc.contributor.author | BEVANS-FONTI, Shannon | - |
dc.contributor.author | GAY, Jason | - |
dc.contributor.author | SUSSAN, Thomas E. | - |
dc.contributor.author | JUN, Jonathan C. | - |
dc.contributor.author | MYERS, Allen C. | - |
dc.contributor.author | OLIVECRONA, Gunilla | - |
dc.contributor.author | SCHWARTZ, Alan R. | - |
dc.contributor.author | HALBERG, Nils | - |
dc.contributor.author | SCHERER, Philipp E. | - |
dc.contributor.author | SEMENZA, Gregg L. | - |
dc.contributor.author | POWELL, David R. | - |
dc.contributor.author | POLOTSKY, Vsevolod Y. | - |
dc.date.accessioned | 2013-09-23T16:53:27Z | - |
dc.date.available | 2013-09-23T16:53:27Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, v.188, n.2, p.240-248, 2013 | - |
dc.identifier.issn | 1073-449X | - |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/2342 | - |
dc.description.abstract | Rationale: Obstructive sleep apnea is a risk factor for dyslipidemia and atherosclerosis, which have been attributed to chronic intermittent hypoxia (CIH). Intermittent hypoxia inhibits a key enzyme of lipoprotein clearance, lipoprotein lipase, and up-regulates a lipoprotein lipase inhibitor, angiopoietin-like 4 (Angptl4), in adipose tissue. The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown. Objectives: To examine whether CIH induces dyslipidemia and atherosclerosis by increasing adipose Angptl4 via hypoxia-inducible factor-1 (HIF-1). Methods: ApoE(-/-) mice were exposed to intermittent hypoxia or air for 4 weeks while being treated with Angptl4-neutralizing antibody or vehicle. Measurements and Main Results: In vehicle-treated mice, hypoxia increased adipose Angptl4 levels, inhibited adipose lipoprotein lipase, increased fasting levels of plasma triglycerides and very low density lipoprotein cholesterol, and increased the size of atherosclerotic plaques. The effects of CIH were abolished by the antibody. Hypoxia-induced increases in plasma fasting triglycerides and adipose Angptl4 were not observed in mice with germline heterozygosity for a HIF-1 alpha knockout allele. Transgenic overexpression of HIF-1 alpha in adipose tissue led to dyslipidemia and increased levels of adipose Angptl4. In cultured adipocytes, constitutive expression of HIF-1 alpha increased Angptl4 levels, which was abolished by siRNA. Finally, in obese patients undergoing bariatric surgery, the severity of nocturnal hypoxemia predicted Angptl4 levels in subcutaneous adipose tissue. Conclusions: HIF-1-mediated increase in adipose Angptl4 and the ensuing lipoprotein lipase in activation may contribute to atherosclerosis in patients with sleep apnea. | - |
dc.description.sponsorship | Mid-Atlantic Nutrition Obesity Research Center (NORC) of Maryland National Institutes of Health (NIH) [P30 DK072488] | - |
dc.description.sponsorship | Johns Hopkins Bayview Clinical Research Unit (NIH-National Institutes of Health) [M01-RR02719] | - |
dc.description.sponsorship | National Institutes of Health (NIH) [HL080105, HL084945, HL109475] | - |
dc.description.sponsorship | American Heart Association [10GRNT3360001, 12POST118200001] | - |
dc.language.iso | eng | - |
dc.publisher | AMER THORACIC SOC | - |
dc.relation.ispartof | American Journal of Respiratory and Critical Care Medicine | - |
dc.rights | restrictedAccess | - |
dc.subject | sleep apnea | - |
dc.subject | lipoprotein clearance | - |
dc.subject | adipose tissue | - |
dc.subject | hypoxia-inducible factor-1 | - |
dc.subject.other | obstructive sleep-apnea | - |
dc.subject.other | positive airway pressure | - |
dc.subject.other | inducible factor 1-alpha | - |
dc.subject.other | lipoprotein-lipase | - |
dc.subject.other | nonfasting triglycerides | - |
dc.subject.other | insulin-resistance | - |
dc.subject.other | knockout mice | - |
dc.subject.other | early signs | - |
dc.subject.other | risk-factor | - |
dc.subject.other | tissue | - |
dc.title | Chronic Intermittent Hypoxia Induces Atherosclerosis via Activation of Adipose Angiopoietin-like 4 | - |
dc.type | article | - |
dc.rights.holder | Copyright AMER THORACIC SOC | - |
dc.identifier.doi | 10.1164/rccm.201209-1688OC | - |
dc.identifier.pmid | 23328524 | - |
dc.subject.wos | Critical Care Medicine | - |
dc.subject.wos | Respiratory System | - |
dc.type.category | original article | - |
dc.type.version | publishedVersion | - |
hcfmusp.author.external | YAO, Qiaoling:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | HERNANDEZ, Karen L.:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA; Univ Miami, Coral Gables, FL 33124 USA | - |
hcfmusp.author.external | SHIN, Mi-Kyung:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | BEVANS-FONTI, Shannon:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | GAY, Jason:Lexicon Pharmaceut Inc, The Woodlands, TX USA | - |
hcfmusp.author.external | SUSSAN, Thomas E.:Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | JUN, Jonathan C.:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | MYERS, Allen C.:Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | OLIVECRONA, Gunilla:Umea Univ, Dept Med Biosci Physiol Chem, Umea, Sweden | - |
hcfmusp.author.external | SCHWARTZ, Alan R.:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | HALBERG, Nils:Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA | - |
hcfmusp.author.external | SCHERER, Philipp E.:Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA | - |
hcfmusp.author.external | SEMENZA, Gregg L.:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Vasc Program, Baltimore, MD 21224 USA | - |
hcfmusp.author.external | POWELL, David R.:Lexicon Pharmaceut Inc, The Woodlands, TX USA | - |
hcfmusp.author.external | POLOTSKY, Vsevolod Y.:Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA | - |
hcfmusp.description.beginpage | 240 | - |
hcfmusp.description.endpage | 248 | - |
hcfmusp.description.issue | 2 | - |
hcfmusp.description.volume | 188 | - |
hcfmusp.origem | WOS | - |
hcfmusp.origem.id | 2-s2.0-84875844834 | - |
hcfmusp.origem.id | WOS:000321817400019 | - |
hcfmusp.publisher.city | NEW YORK | - |
hcfmusp.publisher.country | USA | - |
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dc.description.index | MEDLINE | - |
hcfmusp.remissive.sponsorship | NIH | - |
hcfmusp.citation.scopus | 140 | - |
hcfmusp.scopus.lastupdate | 2024-04-12 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/09 Artigos e Materiais de Revistas Científicas - ODS/03 |
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