Rubiś Paweł, Wiśniowska-Śmiałek Sylwia, Dziewięcka Ewa, Rudnicka-Sosin Lucyna, Kozanecki Artur, Podolec Piotr
Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.
Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.
Adv Med Sci. 2018 Mar;63(1):160-166. doi: 10.1016/j.advms.2017.10.004. Epub 2017 Nov 6.
Serum markers of fibrosis provide an insight into extracellular matrix (ECM) fibrosis in heart failure (HF) and dilated cardiomyopathy (DCM). However, their role as predictors of cardiovascular (CV) events in DCM is poorly understood.
This is an observational, prospective cohort study. 70 DCM patients (48±12.1years, ejection fraction - EF 24.4±7.4) were recruited. Markers of collagen type I and III synthesis - procollagen type I and III carboxy- and amino-terminal peptides (PICP, PIIICP, PINP, PIIINP), fibrosis controlling factors - ostepontin (OPN), transforming growth factor (TGF1-β) and connective tissue growth factor (CTGF), and matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor (TIMP-1), were measured in serum. All patients underwent endomyocardial biopsy. The end-point was combined with CV death and urgent HF hospitalization. Patients were divided into two groups: those who did (group 1, n=45) and did not reach (group 2, n=25) an end-point.
Over a 12-month period of observation, 6 CV deaths and 19 HF hospitalizations occurred. Qualitative and quantitative measures of ECM fibrosis were similar in both groups. The levels of all of the markers of collagen synthesis, TGF1-β, MMP-9 and TIMP-1 were similar, however, OPN, CTGF and MMP-2 were significantly lower in group 1.
Invasively-determined fibrosis levels were not related with CV outcomes in DCM. Out of the 11 markers of fibrosis under study, only OPN was found to be related to CV outcomes. OPN is not only the pivotal protein controlling fibrosis, but may also serve as a biomarker associated with prognosis.
纤维化血清标志物有助于了解心力衰竭（HF）和扩张型心肌病（DCM）中的细胞外基质（ECM）纤维化情况。然而，它们作为DCM中心血管（CV）事件预测指标的作用尚不清楚。
这是一项观察性前瞻性队列研究。招募了70例DCM患者（年龄48±12.1岁，射血分数-EF为24.4±7.4）。检测血清中I型和III型胶原蛋白合成标志物——I型和III型前胶原羧基末端和氨基末端肽（PICP、PIIICP、PINP、PIIINP）、纤维化控制因子——骨桥蛋白（OPN）、转化生长因子（TGF1-β）和结缔组织生长因子（CTGF），以及基质金属蛋白酶（MMP-2、MMP-9）和组织抑制剂（TIMP-1）。所有患者均接受心内膜心肌活检。终点为CV死亡和紧急HF住院的联合情况。患者分为两组：达到终点的患者（第1组，n = 45）和未达到终点的患者（第2组，n = 25）。
在12个月的观察期内，发生了6例CV死亡和19次HF住院。两组ECM纤维化的定性和定量指标相似。所有胶原蛋白合成标志物、TGF1-β、MMP-9和TIMP-1的水平相似，然而，第1组中的OPN、CTGF和MMP-2显著较低。
在DCM中，通过侵入性方法确定的纤维化水平与CV结局无关。在所研究的11种纤维化标志物中，仅发现OPN与CV结局相关。OPN不仅是控制纤维化的关键蛋白，还可能作为与预后相关的生物标志物。
