Nanoliposomes restore endothelial function of human adipose arterioles exposed to AL amyloidosis light chain proteins

Abstract

AL amyloidosis light chain proteins (LC) induce endothelial dysfunction and tissue injury. Nanoliposomes (NL) are <100 nM phospholipid vesicles that could bind amyloid proteins. We tested whether NL can protect against LC induced endothelial dysfunction.MethodsNL from cholesterol, sphingomyelin (1:1) and 5% phosphatidic acid were prepared by probe sonication. Subcutaneous adipose arterioles from patients without amyloidosis/vascular disease were cannulated. Baseline dilator response was measured (acetylcholine 10−9–10−4M and papaverine 10−4M, n=11). A second response followed 1 hour exposure to LC (20 μg/mL from AL patients’ urine, n=6) or LC+NL (1:1 mass, n=5). LC (20 μg) were also mixed with NL at 1:1, 1:5 and 1:10 mass ratios, centrifuged and the supernatant tested by Western blot using antibody to LC.ResultsLC caused impaired dilation to acetylcholine (10−4M: 49±6% vs. 89±4% control, p=0.003); the papaverine response was not different. NL restored dilator response to acetylcholine (10− 4M: 94±3%, p=NS vs. control, p<0.001 vs. LC). Western blot showed progressive reduction of soluble LC with increasing doses of NL suggesting physical sequestration by NL.ConclusionsNL protected human adipose arterioles against LC induced endothelial dysfunction, possibly through sequestration of LC. This proof of concept finding supports exploring use of NL to treat AL amyloid tissue injury.