Biomechanical defects and rescue of cardiomyocytes expressing pathologic nuclear lamins.

ABSTRACT:

Aims

Given the clinical impact of LMNA cardiomyopathies, understanding lamin function will fulfill a clinical need and will lead to advancement in the treatment of heart failure. A multidisciplinary approach combining cell biology, atomic force microscopy (AFM), and molecular modeling was used to analyse the biomechanical properties of human lamin A/C gene (LMNA) mutations (E161K, D192G, N195K) using an in vitro neonatal rat ventricular myocyte model.

Methods and results

The severity of biomechanical defects due to the three LMNA mutations correlated with the severity of the clinical phenotype. AFM and molecular modeling identified distinctive biomechanical and structural changes, with increasing severity from E161K to N195K and D192G, respectively. Additionally, the biomech

SUBMITTER: Laurini E 

PROVIDER: S-EPMC5909658 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature