A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis.

Abstract

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. We have exploited the nematode Caenorhabditis elegans as a novel tool, because its pharynx is evolutionarily related to the vertebrate heart. Our data demonstrate 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.

• Authors: Luisa Diomede, Paola Rognoni, Francesca Lavatelli, Margherita Romeo, Elena del Favero, Laura Cantù, Elena Ghibaudi, Andrea di Fonzo, Alessandro Corbelli, Fabio Fiordaliso, Giovanni Palladini, Veronica Valentini, Vittorio Perfetti, Mario Salmona, Giampaolo Merlini
• Journal: Blood (Blood) Vol. 123 Issue 23 Pg. 3543-52 (Jun 05 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24665135 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Cardiotoxins
• Immunoglobulin Light Chains

Topics

• Adult
• Aged
• Amyloidosis (diagnosis, immunology)
• Animals
• Biological Assay
• Caenorhabditis elegans
• Cardiotoxins (isolation & purification, pharmacology)
• Cell Survival (drug effects)
• Female
• Heart Diseases (diagnosis, immunology)
• Humans
• Immunoglobulin Light Chains (immunology)
• Male
• Middle Aged
• Multiple Myeloma (immunology)
• Pharynx (cytology, drug effects, physiology)