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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9368958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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