Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips - PubMed
6 hours ago
- #PKD2 Deficiency
- #Cardiomyopathy
- #Stem Cell Models
- The study investigates how PKD2 (polycystin-2) deficiency leads to cardiomyopathies in autosomal dominant polycystic kidney disease (ADPKD) patients using human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and 3D bioengineered ventricular cardiac tissue strips (hvCTS).
- PKD2 knockdown in these models resulted in decreased contractile force and slower contraction/relaxation velocities, indicating contractile dysfunction.
- Mechanisms identified include elevated endoplasmic reticulum (ER) stress and reduced activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA), contributing to the contractile defects.
- Interventions with small molecular chaperones (4-phenylbutyrate/tauroursodeoxycholic acid) to alleviate ER stress or CDN1163 to stimulate SERCA activity partially rescued the contractile dysfunction in hvCTS.
- The findings highlight the role of ER stress and SERCA dysfunction in PKD2 deficiency-associated cardiomyopathies, offering insights for potential therapeutic strategies.