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Related Experiment Video

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Dysfunctional HDL in acute stroke.

Guadalupe Ortiz-Munoz1, David Couret2, Bertrand Lapergue3

  • 1Inserm, UMR1148, Paris, F-75018, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75018, France.

Atherosclerosis
|September 4, 2016
PubMed
Summary

High-density lipoprotein (HDL) function is altered in acute cerebral infarction (ACI). Impaired HDL protection of endothelial cells may contribute to ischemic stroke, highlighting potential therapeutic targets.

Keywords:
Endothelial dysfunctionHDLLipoproteinMatrix metalloproteinasesOxidation

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Area of Science:

  • Biochemistry
  • Cardiovascular Science
  • Neurology

Background:

  • High-density lipoprotein (HDL)-cholesterol is a known negative risk factor for acute cerebral infarction (ACI).
  • The study investigates alterations in lipoprotein profiles and HDL functionality during the acute phase of ischemic stroke.

Purpose of the Study:

  • To determine if lipoprotein profiles and HDL functionality are modified in patients experiencing acute cerebral infarction.
  • To assess the impact of these modifications on endothelial cell protection under ischemic conditions.

Main Methods:

  • Blood samples collected from ACI patients within 4.5 hours of symptom onset.
  • Lipoprotein particle size determined by electrophoresis; HDLs isolated via ultracentrifugation.
  • Protein composition (PON1, AAT, MPO) analyzed by Western blot; HDL function assessed using human-brain endothelial cells.

Main Results:

  • ACI patients exhibited a higher proportion of large HDL particles compared to controls.
  • HDLs from ACI patients showed reduced levels of ApoA1 and PON1, but increased MPO and AAT.
  • Patient-derived HDLs were less effective in inhibiting TNFα-induced VCAM1, MCP1, and MMP3 gene expression in endothelial cells.

Conclusions:

  • Acute cerebral infarction is associated with altered HDL particle distribution and protein composition.
  • These modifications result in diminished HDL-mediated protection of endothelial cells, potentially exacerbating ischemic conditions.