Myosin binding protein H-like (MYBPHL): a promising biomarker to predict atrial damage

Abstract

Myosin binding protein H-like (MYBPHL) is a protein associated with myofilament structures in atrial tissue. The protein exists in two isoforms that share an identical amino acid sequence except for a deletion of 23 amino acids in isoform 2. In this study, MYBPHL was found to be expressed preferentially in atrial tissue. The expression of isoform 2 was almost exclusively restricted to the atria and barely detectable in the ventricle, arteria mammaria interna, and skeletal muscle. After atrial damage induced by cryo- or radiofrequency ablation, MYBPHL was rapidly and specifically released into the peripheral circulation in a time-dependent manner. The plasma MYBPHL concentration remained substantially elevated up to 24 hours after the arrival of patients at the intensive care unit. In addition, the recorded MYBPHL values were strongly correlated with those of the established biomarker CK-MB. In contrast, an increase in MYBPHL levels was not evident in patients undergoing aortic valve replacement or transcatheter aortic valve implantation. In these patients, the values remained virtually constant and never exceeded the concentration in the plasma of healthy controls. Our findings suggest that MYBPHL can be used as a precise and reliable biomarker to specifically predict atrial myocardial damage.

Figure 1

Expression of candidate genes in different tissues of the human heart. (A) Expression of candidate genes in left and right atrium (n = 3 each). Values represent the fold-change of gene expression compared to left ventricle. (B–D) Determination of the relative protein amount indicated as label-free quantification intensity of MYBPHL (B), PAM (C) and FHL2 (D) in 16 different regions of the human heart. Ao: aorta, AV: aortic valve, RCA: right coronary artery, LA: left atrium, LCA: left coronary artery, LV: left ventricle, MV: mitral valve, PA: pulmonary artery, PV: pulmonary valve, Pve: pulmonary vein, RA: right atrium, RV: right ventricle, SepA: atrial septum, SepV: ventricular septum, TV: tricuspid valve, IVC: inferior vena cava.

Figure 2

MYPHL isoform 2 is specifically expressed in human atrial tissue. (A) Structure of MYBPHL isoforms 1 and 2. non-coding regions, deleted in isoform 2. Arrows indicate the location of primers used to amplify MYBPHL (black arrows), isoform 1 (green arrows) or isoform 2 (red arrows). (B) Gene expression in human LA, LV, arteria mammaria interna and skeletal muscle tissue. In each slot of the gel 20 µL of amplified fragments were loaded. (C) Quantification of relative gene expression in LA vs. LV, arteria mammaria interna and skeletal muscle tissue. Values are expressed as the mean ± SE. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 3

MYBPHL protein in plasma is increased after atrial damage. (A) Time course of MYBPHL in patients with atrial fibrillation receiving cryo-ablation (n = 17). (B,C) Time course of MYBPHL expression in atrial fibrillation patients with endo- (B) (n = 12) or epicardial (C) (n = 5) cryo-ablation. (D–F) Correlation between MYBPHL and CK-MB. Values are presented as the mean ± SEM. *p < 0.05, **p < 0.01.

Figure 4

MYBPHL is not increased in plasma of patients without atrial damage. (A) Comparison of MYBPHL concentration in plasma of healthy volunteers (n = 11) with pre-OP values of patients with myocardial injury (n = 17). (B,C) Time course of MYBPHL in patients with AVR (B) (n = 5) or TAVI (C) (n = 5). The red line represents the mean concentration of MYBPHL in plasma of healthy controls. Values are presented as the mean ± SEM. n.s.: not significant.