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

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.

Keywords

• cMyBP‐C
• diastolic dysfunction
• S‐glutathionylation