Nair Nandini, Gongora Enrique
Division of Cardiology, Scott and White Memorial Hospital, Temple, TX, USA.
Division of Cardiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
J Circ Biomark. 2018 Jan 19;7:1849454417751735. doi: 10.1177/1849454417751735. eCollection 2018 Jan-Dec.
Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies. Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic Peptide (BNP) was measured as per core laboratory protocol assay at Scott and White Memorial Hospital core laboratory. Correlation analysis was performed between GDF-15 and each of the MMPs-MMP2, MMP3, MMP9, and TIMP as well as New York Heart Association (NYHA) class and echocardiographic parameters (left ventricular ejection fraction (LVEF) and left ventricular internal dimension in diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional echocardiography. The protocol was approved by Scott and White Memorial Hospital Institutional Review Board (S&W IRB). Correlation analysis of control versus all DCM patients showed a strong correlation of GDF-15 with TIMP1 ( = 0.83, < 0.0001) and weaker correlation with MMP3 ( = 0.41, = 0.011) and MMP2 ( = 0.47, = 0.003). MMP9 showed poor correlation with GDF-15 ( = 0.3036, = 0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio ( = -0.47, = 0.006). sST2 correlated strongly with GDF-15 ( = 0.7, < 0.0001). GDF-15 correlated negatively with LVEF ( = -0.49, = 0.004) and positively with LVIDd ( = 0.58, = 0.0006). GDF-15 showed significant positive correlation with NYHA functional class ( = 0.71, < 0.00001) and BNP ( = 0.86, < 0.00001). Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class reported here for the first time in nonischemic dilated hearts may open up new avenues of investigations to better understand molecular mechanisms controlling cardiac remodeling. This study is limited by its small size and needs validation in larger populations.
生长分化因子15（GDF - 15）与纤维化、炎症及心室重塑有关。GDF - 15在特发性扩张型心肌病（DCM）心脏重塑调节中的作用仍不清楚。本研究旨在分析GDF - 15与纤维化标志物之间的分子相互作用及其与心功能恶化的正相关性。研究对象包括24例DCM患者和8例对照者。所有DCM患者冠状动脉造影检查均正常。采用酶联免疫吸附测定法测定血浆中GDF - 15、基质金属蛋白酶2（MMP2）、MMP3、MMP9、MMP组织抑制剂1（TIMP1）和可溶性肿瘤抑制因子2蛋白（sST2）的水平。按照斯科特与怀特纪念医院核心实验室的核心实验室方案测定脑钠肽（BNP）。对GDF - 15与各MMP（MMP2、MMP3、MMP9和TIMP）以及纽约心脏协会（NYHA）心功能分级和超声心动图参数（左心室射血分数（LVEF）和舒张末期左心室内径（LVIDd））进行相关性分析。LVEF和LVIDd通过二维超声心动图获得。该方案经斯科特与怀特纪念医院机构审查委员会（S&W IRB）批准。对照者与所有DCM患者的相关性分析显示，GDF - 15与TIMP1呈强相关（= 0.83，< 0.0001），与MMP3呈较弱相关（= 0.41，= 0.011），与MMP2呈较弱相关（= 0.47，= 0.003）。MMP9与GDF - 15的相关性较差（= 0.3036，= 0.046）。GDF - 15与MMP2/TIMP1比值呈负相关（= -0.47，= 0.006）。sST2与GDF - 15呈强相关（= 0.7，< 0.0001）。GDF - 15与LVEF呈负相关（= -0.49，= 0.004），与LVIDd呈正相关（= 0.58，= 0.0006）。GDF - 15与NYHA心功能分级呈显著正相关（=
