ecfc6dcd684034c77c184532db6d43c1 290563.pdf 5c4b5e1c96c92e9f0202f479f435c8550d7514b7 290563.pdf 7e79fb500835729778390bf112ed7815093d4dc9b235cdef3e736c64aa0bb5f4 290563.pdf Title: Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model Subject: 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. Keywords: HDL dysfunction; hypercholesterolemia; diet; statin; pig Author: Leonie Schoch, Pablo Sutelman, Rosa Suades, Laura Casani, Teresa Padro, Lina Badimon and Gemma Vilahur Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Aug 2 15:46:49 2022 CEST ModDate: Tue Aug 2 15:49:05 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4068799 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UFWERI+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 HZFEOC+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 AUYXKQ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 23 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 41 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C 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Destination: subsection.2.1 Item: Title: Impact of Diet and Rosuvastatin on HDL Function Destination: subsection.2.2 Children: Item: Title: HDL Cholesterol Efflux Capacity Destination: subsubsection.2.2.1 Item: Title: HDL Antioxidant Index Destination: subsubsection.2.2.2 Item: Title: Formation of Conjugated Dienes Destination: subsubsection.2.2.3 Item: Title: Liver HMG-CoA Reductase Activity Destination: subsection.2.3 Item: Title: Impact of Diet and Rosuvastatin on HDL Particle Number Destination: subsection.2.4 Item: Title: Impact of Diet and Rosuvastatin on HDL Apolipoprotein Content Destination: subsection.2.5 Item: Title: Animal Follow-Up Destination: subsection.2.6 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Experimental Design Destination: subsection.4.1 Item: Title: Lipoprotein Particle Isolation Destination: subsection.4.2 Item: Title: Assessment of HDL Functionality Destination: subsection.4.3 Children: Item: Title: HDL Cholesterol Efflux Capacity Destination: subsubsection.4.3.1 Item: Title: HDL Antioxidant Index Destination: subsubsection.4.3.2 Item: Title: Accumulation of Conjugated Dienes in LDL Particles (Lipid Oxidation) Destination: subsubsection.4.3.3 Item: Title: HDL Particle Number by NMR Destination: subsection.4.4 Item: Title: HDL Content of Apolipoproteins Destination: subsection.4.5 Item: Title: HMG-CoA Reductase Activity Destination: subsection.4.6 Item: Title: Follow-Up of Biochemical and Hematological Parameters Destination: subsection.4.7 Item: Title: Statistics Destination: subsection.4.8 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model Author: Leonie Schoch, Pablo Sutelman, Rosa Suades, Laura Casani, Teresa Padro, Lina Badimon and Gemma Vilahur Subject: 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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