title: Dysfunctional HDL in acute stroke.
abstract: HDL-cholesterol concentration is a reliable negative risk factor for acute cerebral infarction (ACI). Beyond quantitative aspects, our aim was to determine whether lipoprotein profiles and HDL functionality were altered at the acute phase of ischemic stroke.
  
  
  
  Blood was taken from ACI patients within 4.5 h of symptom onset. Lipoproteins were separated by electrophoresis for determination of particle size. HDLs were isolated from plasma of patients (n = 10) and controls (n = 10) by ultracentrifugation. The relative amounts of paraoxonase 1 (PON1), α1antitrypsin (AAT) and myeloperoxidase (MPO) were determined by Western blot. HDL functional assays were performed on human-brain endothelial cells stimulated with TNFα.
  
  
  
  Stroke patients had higher proportion of large HDL particles relative to controls (37.8 ± 11.8 vs. 28.4 ± 6.6, p = 0.04). HDLs from patients contained significantly less ApoA1 (1.63 ± 0.42 vs. 2.54 ± 0.71 mg/mL, p = 0.0026) and PON1 (4598 ± 1921 vs. 6598 ± 1127 AU, p = 0.01) than those from controls, whereas MPO and AAT were more abundant in HDLs isolated from ACI patients (respectively 3657 ± 1457 vs. 2012 ± 1234 and 3347 ± 917 vs. 2472 ± 470 AU, p = 0.014 and p = 0.015). HDLs reduced the expression of VCAM1, MCP1 and MMP3 mRNA induced by TNFα in blood-brain barrier endothelial cells. HDLs from patients were less effective in inhibiting TNFα-induced transcription of these genes (respectively 38.6 vs. 55.6% for VCAM1, p = 0.047, 44 vs. 48.1% for MCP1, p = 0.015 and 70 vs. 74% for MMP3, p = 0.024).
  
  
  
  ACI may be associated with a modified distribution of HDL particles (increased proportion of large particles) and HDL-binding proteins, resulting in an inappropriate protection of endothelial cells under ischemic conditions.
authors: Inserm, UMR1148, Paris, F-75018, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75018, France.
authors: Guadalupe
authors: G
authors: Ortiz-Munoz
authors: Inserm, UMR 1188, Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Plateforme CYROI, Sainte-Clotilde, F-97490, France; Université de La Réunion, UMR 1188, Sainte-Clotilde, F-97490, France; CHU de La Réunion, Saint-Pierre, France.
authors: David
authors: D
authors: Couret
authors: Inserm, UMR1148, Paris, F-75018, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75018, France; AP-HP, Department of Neurology, Bichat Stroke Center, Paris, F-75018, France.
authors: Bertrand
authors: B
authors: Lapergue
authors: AP-HP, CHU La Pitié Salpétrière, Paris, F-75013, France.
authors: Eric
authors: E
authors: Bruckert
authors: Inserm, UMR1148, Paris, F-75018, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75018, France; AP-HP, Department of Neurology, Bichat Stroke Center, Paris, F-75018, France.
authors: Elena
authors: E
authors: Meseguer
authors: Inserm, UMR1148, Paris, F-75018, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75018, France; AP-HP, Department of Neurology, Bichat Stroke Center, Paris, F-75018, France.
authors: Pierre
authors: P
authors: Amarenco
authors: Inserm, UMR 1188, Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Plateforme CYROI, Sainte-Clotilde, F-97490, France; Université de La Réunion, UMR 1188, Sainte-Clotilde, F-97490, France; CHU de La Réunion, Saint-Pierre, France. Electronic address: olivier.meilhac@inserm.fr.
authors: Olivier
authors: O
authors: Meilhac
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood; D020520:Brain Infarction / Q000097:blood; D002545:Brain Ischemia / Q000097:blood; D016022:Case-Control Studies; D004586:Electrophoresis; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D009195:Peroxidase / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D020521:Stroke / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D009195:Peroxidase; D043303:Aryldialkylphosphatase
keywords: Endothelial dysfunction; HDL; Lipoprotein; Matrix metalloproteinases; Oxidation