In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
Abstract:
Introduction: Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein localized to the crossbridge-containing C zones of striated muscle sarcomeres, contributing to regulate cardiac contraction and relaxation. Phosphorylation status of cMyBP-C determines cardiac function, and S-glutathionylation of cMyBP-C is increased in human heart failure (HF). In animal models, we demonstrated that elevated S-glutathionylation of cMyBP-C but not phosphorylation correlates with diastolic dysfunction (DD). Hypothesis: S-glutathionylated cMyBP-C would be a biomarker for DD. Methods: Humans, African Green monkeys, and mice with DD determined by echocardiography (E/e’ ratio 〉 X) were matched by age and gender to controls. Blood samples were acquired and analyzed for S-glutathionylated cMyBP-C by immunoblotting. Results: Circulating S-glutathionylated cMyBP-C in DD patients (N=28) was elevated (fold, 1.57± 0.12, P 〈 0.01, t-test) when compared to controls (N=16). We confirmed these results in mice and monkeys with DD demonstrated by echocardiography. In DD monkeys (N=6), the circulated S-glutathionylated cMyBP-C levels were upregulated (fold, 2.7 ± 0.57, P 〈 0.05, t-test) as compared to those in control (CTL) monkeys (N=6). Similarly, S-glutathionylated cMyBP-C was elevated (fold, 1.61 ± 0.23, P 〈 0.05, t-test) in mice with DD (N=5) as compared to controls (N=5). Conclusions: Glutathionylated cMyBP-C has been associated with DD in animal models, and circulating glutathionylated cMyBP-C was elevated in humans, monkeys, and mice with DD. Glutathionylated cMyBP-C may represent a disease-specific biomarker for the presence of DD.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.144.suppl_1.11400
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
1466401-X
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