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Hyperphosphorylation of sarcomeric proteins in heart failure with preserved ejection fraction: selective reversal of PKC hyperactivity by cell therapy

ABSTRACT: Phosphorylation of sarcomeric proteins has been implicated in heart failure with preserved ejection fraction (HFpEF); such changes may contribute to diastolic dysfunction by altering contractility, cardiac stiffness, Ca2+-sensitivity and mechanosensing. Treatment with cardiosphere-derived cells (CDCs) restores normal diastolic function, attenuates fibrosis and inflammation, and improves survival in a rat HFpEF model. Here, we quantified the phosphorylation changes that underlie HFpEF and those reversed by CDC therapy, with a focus on the sarcomeric subproteome.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Heart Left Ventricle

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Vidya Venkatraman

LAB HEAD: Dr. Jennifer Van Eyk

PROVIDER: PXD025555 | Pride | 2022-04-23

REPOSITORIES: Pride

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Myofilament Phosphorylation in Stem Cell Treated Diastolic Heart Failure.

Soetkamp Daniel D Gallet Romain R Parker Sarah J SJ Holewinski Ronald R Venkatraman Vidya V Peck Kiel K Goldhaber Joshua I JI Marbán Eduardo E Van Eyk Jennifer E JE

Circulation research 20211013 12

<h4>Rationale</h4>Phosphorylation of sarcomeric proteins has been implicated in heart failure with preserved ejection fraction (HFpEF); such changes may contribute to diastolic dysfunction by altering contractility, cardiac stiffness, Ca<sup>2+</sup>-sensitivity, and mechanosensing. Treatment with cardiosphere-derived cells (CDCs) restores normal diastolic function, attenuates fibrosis and inflammation, and improves survival in a rat HFpEF model.<h4>Objective</h4>Phosphorylation changes that und ...[more]

PMID: 34641704

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