The right ventricular fibroblast secretome drives cardiomyocyte dedifferentiation

PloS One
Danielle R BrunsLori A Walker

Abstract

In virtually all models of heart failure, prognosis is determined by right ventricular (RV) function; thus, understanding the cellular mechanisms contributing to RV dysfunction is critical. Whole organ remodeling is associated with cell-specific changes, including cardiomyocyte dedifferentiation and activation of cardiac fibroblasts (Cfib) which in turn is linked to disorganization of cytoskeletal proteins and loss of sarcomeric structures. However, how these cellular changes contribute to RV function remains unknown. We've previously shown significant organ-level RV dysfunction in a large animal model of pulmonary hypertension (PH) which was not mirrored by reduced function of isolated cardiomyocytes. We hypothesized that factors produced by the endogenous Cfib contribute to global RV dysfunction by generating a heterogeneous cellular environment populated by dedifferentiated cells. To determine the effect of Cfib conditioned media (CM) from the PH calf (PH-CM) on adult rat ventricular myocytes (ARVM) in culture. Brief exposure (<2 days) to PH-CM results in rapid, marked dedifferentiation of ARVM to a neonatal-like phenotype exhibiting spontaneous contractile behavior. Dedifferentiated cells maintain viability for over 30 days...Continue Reading

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Citations

Apr 15, 2020·Cardiovascular Research·Robert D BrownKurt R Stenmark
Feb 6, 2020·Current Hypertension Reports·Chike C Nwabuo, Ramachandran S Vasan
Dec 5, 2020·Journal of Molecular and Cellular Cardiology·Yike ZhuRoger Foo
Aug 26, 2021·Scientific Reports·Tereza HavlenovaVojtech Melenovsky

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Datasets Mentioned

BETA
GSE133904

Methods Mentioned

BETA
biopsies
electrophoresis
RNAseq
PCA
RNA-seq
Immunodepletion

Software Mentioned

GSEA
R
Msig
DEseq2
HISAT2
STRINGTIE

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