Depletion of Vasohibin 1 Speeds Contraction and Relaxation in Failing Human Cardiomyocytes.

ABSTRACT:

Rationale

Impaired myocardial relaxation is an intractable feature of several heart failure (HF) causes. In human HF, detyrosinated microtubules stiffen cardiomyocytes and impair relaxation. Yet the identity of detyrosinating enzymes have remained ambiguous, hindering mechanistic study and therapeutic development.

Objective

We aimed to determine if the recently identified complex of VASH1/2 (vasohibin 1/2) and SVBP (small vasohibin binding protein) is an active detyrosinase in cardiomyocytes and if genetic inhibition of VASH-SVBP is sufficient to lower stiffness and improve contractility in HF.

Methods and results

Transcriptional profiling revealed that VASH1 transcript is >10-fold more abundant than VASH2 in human hearts. Using short hairpin RNAs (shRNA

SUBMITTER: Chen CY 

PROVIDER: S-EPMC7334093 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature