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

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-glutathi...

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Published inJournal of the American Heart Association Vol. 11; no. 11; p. e025295
Main Authors Zhou, Xiaoxu, Jeong, Euy-Myoung, Liu, Hong, Kaseer, Bahaa, Liu, Man, Shrestha, Suvash, Imran, Hafiz, Kavanagh, Kylie, Jiang, Ning, Desimone, Lori-Ann, Feng, Feng, Shi, Guangbin, Jeong, Go Eun, Zhou, Anyu, Stockwell, Philip, Dudley, Jr, Samuel C
Format Journal Article
LanguageEnglish
Published England John Wiley and Sons Inc 07.06.2022
Wiley
Subjects
Animals
Biomarkers
Brief Communication
Carrier Proteins - analysis
Carrier Proteins - metabolism
Chlorocebus aethiops
cMyBP‐C
Diastole - physiology
diastolic dysfunction
Heart Diseases - metabolism
Humans
Mice
Myocardial Contraction
Myocardium - metabolism
Phosphorylation
S‐glutathionylation
diastolic dysfunction
S‐glutathionylation
cMyBP‐C
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Summary: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, =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 ( =0.047) in DD monkeys (n=6), and by 1.49 (1.22-2.06)-fold ( =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.
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For Sources of Funding and Disclosures, see page 4.
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.122.025295