Blood-based microRNA profiling in patients with cardiac amyloidosis

PLoS One. 2018 Oct 17;13(10):e0204235. doi: 10.1371/journal.pone.0204235. eCollection 2018.

Abstract

Introduction: Amyloidosis is caused by dysregulation of protein folding resulting in systemic or organ specific amyloid aggregation. When affecting the heart, amyloidosis can cause severe heart failure, which is associated with a high morbidity and mortality. Different subtypes of cardiac amyloidosis exist e.g. transthyretin cardiac amyloidosis and senile cardiac amyloidosis. Today, diagnostics is primarily based on cardiac biopsies and no clinically used circulating blood-based biomarkers existing. Therefore, our aim was to identify circulating microRNAs in patients with different forms of amyloidosis.

Methods: Blood was collected from healthy subjects (n = 10), patients with reduced ejection fraction (EF < 35%; n = 10), patients affected by transthyretin cardiac amyloidosis (n = 13) as well as senile cardiac amyloidosis (n = 11). After performing TaqMan array profiling, promising candidates, in particular miR-99a-5p, miR-122-5p, miR-27a-3p, miR-221-3p, miR-1180-3p, miR-155-5p, miR-339-3p, miR-574-3p, miR-342-3p and miR-329-3p were validated via quantitative real time PCR.

Results: The validation experiments revealed a significant upregulation of miR-339-3p in patients affected with senile cardiac amyloidosis compared to controls. This corresponded to the array profiling results. In contrast, there was no deregulation in the other patient groups.

Conclusion: MiR-339-3p was increased in blood of patients with senile cardiac amyloidosis. Therefore, miR-339-3p is a potential candidate as biomarker for senile cardiac amyloidosis in future studies. Larger patient cohorts should be investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial / blood
  • Amyloid Neuropathies, Familial / genetics
  • Amyloidosis / blood
  • Amyloidosis / genetics*
  • Case-Control Studies
  • Circulating MicroRNA / genetics
  • Female
  • Gene Expression Profiling
  • Genetic Markers
  • Heart Diseases / blood
  • Heart Diseases / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods*
  • Up-Regulation*

Substances

  • Circulating MicroRNA
  • Genetic Markers
  • MIRN339 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related