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dc.contributor.author
Feng, Ma
dc.contributor.author
Darabi, Maryam
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Tubeuf, Emilie
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Canicio, Aurélie
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Lhomme, Marie
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Frisdal, Eric
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Lanfranchi Lebreton, Sandrine
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Matheron, Lucrèce
dc.contributor.author
Rached, Fabiana
dc.contributor.author
Ponnaiah, Maharajah
dc.contributor.author
Serrano, Carlos V.
dc.contributor.author
Santos, Raul D.
dc.contributor.author
Brites, Fernando Daniel
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Bolbach, Gerard
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Gautier, Emmanuel
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Huby, Thierry
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Carrie, Alain
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Bruckert, Eric
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Guerin, Maryse
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Couvert, Philippe
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Giral, Philippe
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Lesnik, Philippe
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Le Goff, Wilfried
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Guillas, Isabelle
dc.contributor.author
Kontush, Anatol
dc.date.available
2020-09-01T18:01:53Z
dc.date.issued
2019-12
dc.identifier.citation
Feng, Ma; Darabi, Maryam; Tubeuf, Emilie; Canicio, Aurélie; Lhomme, Marie; et al.; Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease; Sage Publications Ltd; European Journal of Preventive Cardiology; 12-2019; 1-11
dc.identifier.issn
2047-4873
dc.identifier.uri
http://hdl.handle.net/11336/112911
dc.description.abstract
Background: Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods: To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results: When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [3H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions: Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Sage Publications Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
APOLIPOPROTEINS
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ATHEROSCLEROSIS
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CETP
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CHYLOMICRONS
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HDL FUNCTION
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HDL METABOLISM
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LCAT
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LIPOPROTEIN LIPASE
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LIPOPROTEIN METABOLISM
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POSTPRANDIAL LIPID METABOLISM
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Otras Ciencias de la Salud
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dc.subject.classification
Ciencias de la Salud
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-07-01T17:12:11Z
dc.journal.pagination
1-11
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Feng, Ma. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Darabi, Maryam. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Tubeuf, Emilie. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Canicio, Aurélie. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Lhomme, Marie. Institute Of Cardiometabolism And Nutrition; Francia
dc.description.fil
Fil: Frisdal, Eric. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Lanfranchi Lebreton, Sandrine. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Matheron, Lucrèce. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Rached, Fabiana. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Ponnaiah, Maharajah. Institute Of Cardiometabolism And Nutrition; Francia
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Fil: Serrano, Carlos V.. Instituto Do Coracao Do Hospital Das Clinicas; Brasil
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Fil: Santos, Raul D.. Instituto Do Coracao Do Hospital Das Clinicas; Brasil
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Fil: Brites, Fernando Daniel. Universidad de Buenos Aires; Argentina. Instituto Do Coracao Do Hospital Das Clinicas; Brasil
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Fil: Bolbach, Gerard. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Gautier, Emmanuel. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Huby, Thierry. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Carrie, Alain. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Bruckert, Eric. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Guerin, Maryse. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Couvert, Philippe. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Giral, Philippe. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Lesnik, Philippe. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Le Goff, Wilfried. Université Pierre et Marie Curie; Francia. Inserm; Francia
dc.description.fil
Fil: Guillas, Isabelle. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.description.fil
Fil: Kontush, Anatol. Inserm; Francia. Université Pierre et Marie Curie; Francia
dc.journal.title
European Journal of Preventive Cardiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1177/2047487319894114
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/2047487319894114
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