Nanoliposomes protect against human arteriole endothelial dysfunction induced by β-amyloid peptide

J Cereb Blood Flow Metab. 2016 Feb;36(2):405-12. doi: 10.1177/0271678X15610134. Epub 2015 Oct 8.

Abstract

We tested whether nanoliposomes containing phosphatidylcholine, cholesterol and phosphatidic acid (NLPA) prevent β-amyloid 1-42 (Aβ42) fibrillation and Aβ42-induced human arteriole endothelial dysfunction. NLPA abolished Aβ42 fibril formation (thioflavin-T fluorescence/electron microscopy). In ex-vivo human adipose and leptomeningeal arterioles, Aβ42 impaired dilator response to acetylcholine that was reversed by NLPA; this protection was abolished by L-NG-nitroarginine methyl ester. Aβ42 reduced human umbilical vein endothelial cell NO production that was restored by NLPA. Nanoliposomes prevented Aβ42 amyloid formation, reversed Aβ42-induced human microvascular endothelial dysfunction and may be useful in Alzheimer's disease.

Keywords: Alzheimer’s disease; Amyloid; endothelial function; liposome; microvasculature.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholine / antagonists & inhibitors
  • Acetylcholine / pharmacology
  • Adipose Tissue / blood supply
  • Amyloid beta-Peptides*
  • Arterioles / pathology*
  • Cholesterol / administration & dosage
  • Cholesterol / therapeutic use
  • Endothelium, Vascular / pathology*
  • Humans
  • In Vitro Techniques
  • Liposomes / therapeutic use*
  • Male
  • Meninges / blood supply
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nanoparticles / therapeutic use
  • Nitric Oxide / biosynthesis
  • Peptide Fragments*
  • Phosphatidic Acids / administration & dosage
  • Phosphatidic Acids / therapeutic use
  • Phosphatidylcholines / administration & dosage
  • Phosphatidylcholines / therapeutic use
  • Vascular Diseases / chemically induced*
  • Vascular Diseases / pathology
  • Vascular Diseases / prevention & control*
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Amyloid beta-Peptides
  • Liposomes
  • Peptide Fragments
  • Phosphatidic Acids
  • Phosphatidylcholines
  • Vasodilator Agents
  • amyloid beta-protein (1-42)
  • Nitric Oxide
  • Cholesterol
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester