PLN Cardiomyopathy

Graphical Abstract

Abstract

Patient-specific  human Induced Pluripotent Stem Cells (hiPSC)-derived cardiomyocytes  (hiPSC-CMs) hold great potential in in vitro disease modelling.  Recently, in vitro research using hiPSC-CMs has focused on finding  molecular mechanisms to understand PLNR14del pathophysiology. These  studies suggested a role of an elevated unfolded protein response and  disturbed metabolic function that resulted in decreased contractility.  However, to our knowledge, the link between contractility, calcium  handling and the profound amount of fibrosis found in the hearts of  PLNR14del patients remains unknown.

Therefore,  in this project, we aim to elucidate the molecular mechanisms related  to the PLNR14del phenotype in a 3D context, by using human Cardiac  Organoids (hCOs). The hCOs technology allows a robust middle-high  throughput screening for novel therapeutic strategies to cure the  PLNR14del disease.

Students involved:

Maud van den Broek, Corné van Dam, Dagmar Duijzer, Lucie Groenendaal, Naomi Jong, Ischa Kalka, Maartje Kievit, Thirza Lapré, Marc Pijper, Rebeca Puscasu, Noa Rijnenveld, Luuc Stoelinga, Aaron Strous, Karlijn aan de Wiel