Phospho-Proteomic Analysis of Cardiac Dyssynchrony and Resynchronization Therapy.

Autor: Stachowski MJ; Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA., Holewinski RJ; Advanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048, USA., Grote E; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Venkatraman V; Advanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048, USA., Van Eyk JE; Advanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048, USA.; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Kirk JA; Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Jazyk: angličtina
Zdroj: Proteomics [Proteomics] 2018 Oct; Vol. 18 (19), pp. e1800079. Date of Electronic Publication: 2018 Aug 30.
DOI: 10.1002/pmic.201800079
Abstrakt: Cardiac dyssynchrony arises from conduction abnormalities during heart failure and worsens morbidity and mortality. Cardiac resynchronization therapy (CRT) re-coordinates contraction using bi-ventricular pacing, but the cellular and molecular mechanisms involved remain largely unknown. The aim is to determine how dyssynchronous heart failure (HF dys ) alters the phospho-proteome and how CRT interacts with this unique phospho-proteome by analyzing Ser/Thr and Tyr phosphorylation. Phospho-enriched myocardium from dog models of Control, HF dys , and CRT is analyzed via MS. There were 209 regulated phospho-sites among 1761 identified sites. Compared to Con and CRT, HF dys is hyper-phosphorylated and tyrosine phosphorylation is more likely to be involved in signaling that increased with HF dys and was exacerbated by CRT. For each regulated site, the most-likely targeting-kinase is predicted, and CK2 is highly specific for sites that are "fixed" by CRT, suggesting activation of CK2 signaling occurs in HF dys that is reversed by CRT, which is supported by western blot analysis. These data elucidate signaling networks and kinases that may be involved and deserve further study. Importantly, a possible role for CK2 modulation in CRT has been identified. This may be harnessed in the future therapeutically to compliment CRT, improving its clinical effects.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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