Varela, Lourdes M.Meseguer, ElenaLapergue, BertrandCouret, DavidAmarenco, PierreMeilhac, Olivier2022-11-212022-11-212020-07-17Varela LM, Meseguer E, Lapergue B, Couret D, Amarenco P, Meilhac O. Changes in High-Density Lipoproteins Related to Outcomes in Patients with Acute Stroke. J Clin Med. 2020 Jul 17;9(7):2269http://hdl.handle.net/10668/4386Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood-brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/HDLStrokeFunctional outcomePON1Blood-brain barrier (BBB) dysfunctionLow-density lipoproteins (LDL) oxidationParaoxonase-1High-density lipoproteinAccidente cerebrovascularLipoproteínas LDLArildialquilfosfatasaLipoproteínas HDLMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Triester Hydrolases::AryldialkylphosphataseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-8Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Protective Agents::AntioxidantsMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Heavy::CopperMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::Selectins::E-SelectinMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::Intercellular Adhesion Molecule-1Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Particle SizeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding ProteinsMedical Subject Headings::Anatomy::Cardiovascular System::Blood-Brain BarrierMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial CellsMedical Subject Headings::Chemicals and Drugs::Lipids::Lipoproteins::Lipoproteins, HDLMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::StrokeMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Non-Narcotic::Anti-Inflammatory Agents, Non-SteroidalMedical Subject Headings::Diseases::Cardiovascular DiseasesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::ElectrophoresisMedical Subject Headings::Chemicals and Drugs::Lipids::Lipoproteins::Lipoproteins, LDLMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Centrifugation::UltracentrifugationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, WesternMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Thrombolytic TherapyMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Acrylamidesresearch article32708891open access10.3390/jcm90722692077-0383PMC7408777