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β‐amyloid Peptide‐Induced Human Arteriole Endothelial Dysfunction is Attenuated by Nanoliposomes
Author(s) -
GuzmanVillanueva Diana,
Madine Jill,
Truran Seth,
Davies Hannah,
Burciu Camelia,
Franco Daniel,
Weissig Volkmar,
Migrino Raymond
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.638.9
Subject(s) - endothelial dysfunction , amyloid (mycology) , arteriole , chemistry , endocrinology , nitric oxide , dilator , medicine , biochemistry , microcirculation , pathology
Microvascular impairment is an under‐recognized pathologic mechanism of misfolded protein diseases and is critical in early Alzheimer's disease (AD). We showed that β‐amyloid 42 (Aβ), a peptide involved in AD, induces endothelial dysfunction in human adipose/leptomeningeal arterioles. Nanoliposomes (NL) are phospholipid containing particles that altered the structural properties of another amyloid protein (AL amyloid light chains) and restored endothelial function. Aim To determine if phosphatidic acid (PA) containing NL (NLPA) prevent Aβ fibril formation and restore endothelial function in human arterioles exposed to Aβ. Methods NLPA (70% cholesterol, 25% phosphatidylcholine, 5% PA) were mixed with Aβ and fibrillation rate measured by thioflavin T fluorescence. Human abdominal subcutaneous adipose arterioles were isolated and constricted with endothelin‐1. Baseline control dilation was measured following acetylcholine (10 ‐9 ‐10 ‐4 M) and papaverine (10 ‐4 M); after washing arterioles were exposed to 2 µM Aβ±NLPA (1:10 mass) and dilator response was measured. Human umbilical vein endothelial cells (HUVEC) were exposed to Aβ±NLPA (24 hrs) and nitric oxide (NO) gas was measured. Results NLPA prevented Aβ fibril formation (F1). Aβ induced impaired dilator response to acetylcholine and papaverine while reducing HUVEC NO (F2). These changes were attenuated by NLPA. Conclusions NL prevent Aβ amyloid fibril formation. NL reduce Aβ‐induced endothelial and non‐endothelial arteriole dysfunction, the former likely by increasing NO. Nanoliposomes represent a novel treatment approach to amyloid protein diseases such as AD.