TY - JOUR
T1 - A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis
AU - Diomede, Luisa
AU - Rognoni, Paola
AU - Lavatelli, Francesca
AU - Romeo, Margherita
AU - Del Favero, Elena
AU - Cantù, Laura
AU - Ghibaudi, Elena
AU - Di Fonzo, Andrea
AU - Corbelli, Alessandro
AU - Fiordaliso, Fabio
AU - Palladini, Giovanni
AU - Valentini, Veronica
AU - Perfetti, Vittorio
AU - Salmona, Mario
AU - Merlini, Giampaolo
PY - 2014/6/5
Y1 - 2014/6/5
N2 - Poor prognosis and limited therapeutic options characterize immunoglobulin light-chain (AL) amyloidosis with major heart involvement. Reliable experimental models are needed to study light-chain (LC)/heart interactions and to explore strategies for prevention of cardiac damage.Wehave exploited the nematode Caenorhabditis elegans as a novel tool, because its pharynx is evolutionarily related to the vertebrate heart. Our datademonstrate that the pharyngeal pumping of C elegans is significantly and selectively reduced by LCs from AL patients suffering from cardiomyopathy, but not by amyloid LCs with different organ tropism or nonamyloidogenic LCs from multiple myeloma. This functional alteration is dependent on the LC concentration and results in persistent pharyngeal dysfunction and in a significant reduction of the worms' lifespan. These manifestations are paralleled by an increase of mitochondrial reactive oxygen species and can be prevented by treatment with antioxidant agents. In conclusion, these data indicate that this nematode-based assay is a promising surrogate model for investigating the heart-specific toxicity of amyloidogenic LCs and for a rapid screening of new therapeutic strategies.
AB - Poor prognosis and limited therapeutic options characterize immunoglobulin light-chain (AL) amyloidosis with major heart involvement. Reliable experimental models are needed to study light-chain (LC)/heart interactions and to explore strategies for prevention of cardiac damage.Wehave exploited the nematode Caenorhabditis elegans as a novel tool, because its pharynx is evolutionarily related to the vertebrate heart. Our datademonstrate that the pharyngeal pumping of C elegans is significantly and selectively reduced by LCs from AL patients suffering from cardiomyopathy, but not by amyloid LCs with different organ tropism or nonamyloidogenic LCs from multiple myeloma. This functional alteration is dependent on the LC concentration and results in persistent pharyngeal dysfunction and in a significant reduction of the worms' lifespan. These manifestations are paralleled by an increase of mitochondrial reactive oxygen species and can be prevented by treatment with antioxidant agents. In conclusion, these data indicate that this nematode-based assay is a promising surrogate model for investigating the heart-specific toxicity of amyloidogenic LCs and for a rapid screening of new therapeutic strategies.
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U2 - 10.1182/blood-2013-10-525634
DO - 10.1182/blood-2013-10-525634
M3 - Article
C2 - 24665135
AN - SCOPUS:84902128559
VL - 123
SP - 3543
EP - 3552
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -