Increased kielin/chordin-like protein levels are associated with the severity of heart failure

Background-Previous studies demonstrated that the transforming growth factor (TGF) beta superfamily, including TGF-beta s and bone morphogenetic proteins (BMPs), plays important roles in cardiovascular diseases. The kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of TGF-beta s and BMPs. However, the role of KCP during heart failure (HF) remains unknown. The present study aimed to investigate the cardiac expression of KCP in human failing hearts. Methods: The human failing heart samples from patients with dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) were collected, and normal heart (n = 8) samples from unmatched donors were collected as controls. Collagen volume, KCP levels, and mRNA levels of several BMPs in left ventricles (LV) of all hearts were measured. Results: The KCP levels were significantly higher in human failing hearts than in normal hearts. KCP levels were positively associated with hypertrophy markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (beta-MHC). In addition, KCP levels were also positively associated with left ventricular end-diastolic dimension (LVEDD), collagen I alpha and collagen III alpha expression but were negatively associated with left ventricular ejection fraction (LVEF). Furthermore, increased TGF-beta 1, BMP2/4/6/10 and reduced BMP7 levels were observed, and positive correlations between KCP and TGF-beta 1 and negative correlation between KCP and BMP2/7 were found, but not for BMP4/6/10. Conclusions: KCP was closely associated with heart failure. The regulation of BMP2/7 and TGF-beta 1 expression may be the possible mechanisms.