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Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10...

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Autores principales: Schoch, Leonie, Sutelman, Pablo, Suades, Rosa, Casani, Laura, Padro, Teresa, Badimon, Lina, Vilahur, Gemma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368958/
https://www.ncbi.nlm.nih.gov/pubmed/35955730
http://dx.doi.org/10.3390/ijms23158596
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author Schoch, Leonie
Sutelman, Pablo
Suades, Rosa
Casani, Laura
Padro, Teresa
Badimon, Lina
Vilahur, Gemma
author_facet Schoch, Leonie
Sutelman, Pablo
Suades, Rosa
Casani, Laura
Padro, Teresa
Badimon, Lina
Vilahur, Gemma
author_sort Schoch, Leonie
collection PubMed
description High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content.
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spelling pubmed-93689582022-08-12 Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model Schoch, Leonie Sutelman, Pablo Suades, Rosa Casani, Laura Padro, Teresa Badimon, Lina Vilahur, Gemma Int J Mol Sci Article High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content. MDPI 2022-08-02 /pmc/articles/PMC9368958/ /pubmed/35955730 http://dx.doi.org/10.3390/ijms23158596 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schoch, Leonie
Sutelman, Pablo
Suades, Rosa
Casani, Laura
Padro, Teresa
Badimon, Lina
Vilahur, Gemma
Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title_full Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title_fullStr Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title_full_unstemmed Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title_short Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model
title_sort hypercholesterolemia-induced hdl dysfunction can be reversed: the impact of diet and statin treatment in a preclinical animal model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368958/
https://www.ncbi.nlm.nih.gov/pubmed/35955730
http://dx.doi.org/10.3390/ijms23158596
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