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 language | English (US) |
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Article number | e025295 |
Journal | Journal of the American Heart Association |
Volume | 11 |
Issue number | 11 |
DOIs | |
State | Published - 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