Circulating S-Glutathionylated cMyBP-C as a Biomarker for Cardiac Diastolic Dysfunction

Xiaoxu Zhou, Euy Myoung Jeong, Hong Liu, Bahaa Kaseer, Man Liu, Suvash Shrestha, Hafiz Imran, Kylie Kavanagh, Ning Jiang, Lori Ann Desimone, Feng Feng, Guangbin Shi, Go Eun Jeong, Anyu Zhou, Philip Stockwell, Samuel C. Dudley

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: cMyBP-C (Cardiac myosin binding protein-C) regulates cardiac contraction and relaxation. Previously, we demonstrated that elevated myocardial S-glutathionylation of cMyBP-C correlates with diastolic dysfunction (DD) in animal models. In this study, we tested whether circulating S-glutathionylated cMyBP-C would be a biomarker for DD. METHODS AND RESULTS: Humans, African Green monkeys, and mice had DD determined by echocardiography. Blood samples were acquired and analyzed for S-glutathionylated cMyBP-C by immunoprecipitation. Circulating S-glutathionylated cMyBP-C in human participants with DD (n=24) was elevated (1.46±0.13-fold, P=0.014) when compared with the non-DD controls (n=13). Similarly, circulating S-glutathionylated cMyBP-C was upregulated by 2.13±0.47-fold (P=0.047) in DD monkeys (n=6), and by 1.49 (1.22–2.06)-fold (P=0.031) in DD mice (n=5) compared with the respective non-DD controls. Circulating S-glutathionylated cMyBP-C was positively correlated with DD in humans. CONCLUSIONS: Circulating S-glutathionylated cMyBP-C was elevated in humans, monkeys, and mice with DD. S-glutathionylated cMyBP-C may represent a novel biomarker for the presence of DD.

Original languageEnglish (US)
Article numbere025295
JournalJournal of the American Heart Association
Volume11
Issue number11
DOIs
StatePublished - Jun 7 2022

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants R01 HL104025 (Dudley), R01 HL106592 (Dudley), NIH UL1TR001420 (Kavanagh), and P40OD010965 (Kavanagh).

Publisher Copyright:
© 2022 The Authors.

Keywords

  • S-glutathionylation
  • cMyBP-C
  • diastolic dysfunction

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