Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes

• DOI: 10.1371/journal.pone.0137716
• Publication Date: 2015-09-22T18:13:00Z
• Authors: Helen P. McWillia...; James S. Foster; Nicole Hackenbrack; Marina Ramirez-Al...; Dallas Donohoe; Angela Williams; Sallie Macy; Craig Wooliver; Dale Wortham; Jennifer Morrell-...; Carmen M. Foster; Stephen J. Kennel; Jonathan S. Wall
• Keywords: Amyloid (mycology); Internalization

Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy a dire consequence, resulting in an extremely poor prognosis. AL characterized by production monoclonal free light chains that deposit as fibrils principally heart, liver, kidneys causing organ dysfunction. We have studied effects fibrils, produced from recombinant λ6 variable domains, on metabolic activity human cardiomyocytes. The data indicate at 0.1 μM, but not monomer, significantly decrease enzymatic cellular NAD(P)H-dependent oxidoreductase, without significant cell death. presence did affect ATP levels; however, oxygen consumption was increased reactive species were detected. Confocal fluorescence microscopy showed bound to remained surface with little fibril internalization. These severely impair cardiomyocyte metabolism dose dependent manner. suggest effective therapeutic intervention for these patients should include methods removing potentially toxic fibrils.