title: Nanoliposomes protect against human arteriole endothelial dysfunction induced by β-amyloid peptide.
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.
authors.affiliation: Phoenix Veterans Affair Health Care System, Phoenix, AZ, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Truran
authors.affiliation: Midwestern University, Glendale, AZ, USA.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Weissig
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Jillian
authors.initials: J
authors.lastname: Madine
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Davies
authors.affiliation: Midwestern University, Glendale, AZ, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Guzman-Villanueva
authors.affiliation: Phoenix Veterans Affair Health Care System, Phoenix, AZ, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Franco
authors.affiliation: Phoenix Veterans Affair Health Care System, Phoenix, AZ, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Karamanova
authors.affiliation: Phoenix Veterans Affair Health Care System, Phoenix, AZ, USA.
authors.forename: Camelia
authors.initials: C
authors.lastname: Burciu
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Geidy
authors.initials: G
authors.lastname: Serrano
authors.affiliation: Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Phoenix Veterans Affair Health Care System, Phoenix, AZ, USA University of Arizona College of Medicine, Phoenix, AZ, USA raymond.migrino@va.gov.
authors.forename: Raymond Q
authors.initials: RQ
authors.lastname: Migrino
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000273:Adipose Tissue / Q000098:blood supply; D016229:Amyloid beta-Peptides; D001160:Arterioles / Q000473:pathology*; D002784:Cholesterol / Q000008:administration & dosage / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000627:therapeutic use*; D008297:Male; D008578:Meninges / Q000098:blood supply; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D053758:Nanoparticles / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis; D010446:Peptide Fragments; D010712:Phosphatidic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000627:therapeutic use; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D014665:Vasodilator Agents; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D002784:Cholesterol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester
keywords: Alzheimer’s disease; Amyloid; endothelial function; liposome; microvasculature