Light chain amyloidosis induced inflammatory changes in cardiomyocytes and adipose-derived mesenchymal stromal cells

Torri L. Jordan, Khansaa Maar, Keely R. Redhage, Pinaki Misra, Luis M. Blancas-Mejia, Christopher J. Dick, Jonathan S. Wall, Angela Williams, Allan B. Dietz, Andre J van Wijnen, Yi Lin, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

Abstract

Light chain (AL) amyloidosis is a progressive, degenerative disease characterized by the misfolding and amyloid deposition of immunoglobulin light chain (LC). The amyloid deposits lead to organ failure and death. Our laboratory is specifically interested in cardiac involvement of AL amyloidosis. We have previously shown that the fibrillar aggregates of LC proteins can be cytotoxic and arrest the growth of human RFP-AC16 cardiomyocytes in vitro. We showed that adipose-derived mesenchymal stromal cells (AMSC) can rescue the cardiomyocytes from the fibril-induced growth arrest through contact-dependent mechanisms. In this study, we examined the transcriptome changes of human cardiomyocytes and AMSC in the presence of AL amyloid fibrils. The presence of fibrils causes a ‘priming’ immune response in AMSC associated with interferon associated genes. Exposure to AL fibrils induced changes in the pathways associated with immune response and extracellular matrix components in cardiomyocytes. We also observed upregulation of innate immune-associated transcripts (chemokines, cytokines, and complement), suggesting that amyloid fibrils initiate an innate immune response on these cells, possibly due to phenotypic transformation. This study corroborates and expands our previous studies and identifies potential new immunologic mechanisms of action for fibril toxicity on human cardiomyocytes and AMSC rescue effect on cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)1383-1393
Number of pages11
JournalLeukemia
Volume34
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Jordan, T. L., Maar, K., Redhage, K. R., Misra, P., Blancas-Mejia, L. M., Dick, C. J., Wall, J. S., Williams, A., Dietz, A. B., van Wijnen, A. J., Lin, Y., & Ramirez-Alvarado, M. (2020). Light chain amyloidosis induced inflammatory changes in cardiomyocytes and adipose-derived mesenchymal stromal cells. Leukemia, 34(5), 1383-1393. https://doi.org/10.1038/s41375-019-0640-4