Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin.
Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin.
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DOI：
10.1161/circulationaha.114.013215
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发表时间：
2015-04-07
期刊：
影响因子：
37.8
通讯作者：
LeWinter MM
中科院分区：
文献类型：
--
作者：
Zile MR;Baicu CF;Ikonomidis JS;Stroud RE;Nietert PJ;Bradshaw AD;Slater R;Palmer BM;Van Buren P;Meyer M;Redfield MM;Bull DA;Granzier HL;LeWinter MM
这项研究的目的是确定心力衰竭和射血分数(HFpEF)保留的患者是否存在被动心肌僵硬的增加，以及所发现的变化在多大程度上依赖于细胞外基质、纤维胶原和/或心肌细胞titin的变化。对70例接受冠状动脉旁路移植术的患者进行了超声心动图、血浆生物标记物测定和术中左室心外膜前壁活检。将患者分为3组：对照组(n=17，无高血压或糖尿病)，高血压(HTN)无(-)HFpEF组(n=31)，HTN伴(+)HFpEF组(n=22)。对活检组织进行了一项或多项研究：被动硬度测量以确定总的、胶原依赖的和肌动蛋白依赖的硬度(差异提取法)、胶原分析(生化或组织学)或肌动蛋白异构体和磷酸化分析。与对照组相比，HTN(-)HFpEF患者的左心室舒张末压(LVEDP)、心肌被动僵硬、心肌胶原和肌动蛋白磷酸化水平无明显变化，但炎症生物标志物(CRP、Sst2、TIMP-1)明显升高。与对照组和HTN(-)HFpEF组比较，HTN(+)HFpEF组LVEDP、左房容积、NT-proBNP、总硬度、胶原和肌动蛋白依赖性硬度、不溶性胶原、PEVK S11878上的Titin磷酸化增加(S26)，N2B S4185上的磷酸化减少(S469)，炎症生物标志物增加。没有HFpEF的高血压患者，不会改变被动心肌僵硬。HTN(+)HFpEF患者的被动心肌僵硬显著增加，胶原依赖和肌动蛋白依赖的僵硬增加。这些数据表明，HFpEF的发展依赖于胶原和肌动蛋白稳态的变化。
The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes are dependent on changes in extracellular matrix fibrillar collagen and/or cardiomyocyte titin. Seventy patients undergoing coronary artery bypass grafting underwent an echocardiogram, plasma biomarker determination, and intra-operative left ventricular (LV) epicardial anterior wall biopsy. Patients were divided into 3 groups: referent control (n=17, no hypertension or diabetes), hypertension (HTN) without(-) HFpEF (n=31), and HTN with(+) HFpEF (n=22). One or more of the following studies were performed on the biopsies: passive stiffness measurements to determine total, collagen-dependent and titin-dependent stiffness (differential extraction assay), collagen assays (biochemistry or histology), or titin isoform and phosphorylation assays. Compared with controls, patients with HTN(-)HFpEF had no change in LV end diastolic pressure (LVEDP), myocardial passive stiffness, collagen, or titin phosphorylation but had an increase in biomarkers of inflammation (CRP, sST2, TIMP-1). Compared with both control and HTN(-)HFpEF, patients with HTN(+)HFpEF had increased LVEDP, left atrial volume, NT-proBNP, total, collagen-dependent and titin-dependent stiffness, insoluble collagen, increased titin phosphorylation on PEVK S11878(S26), reduced phosphorylation on N2B S4185(S469), and increased biomarkers of inflammation. Hypertension in the absence of HFpEF, did not alter passive myocardial stiffness. Patients with HTN(+)HFpEF had a significant increase in passive myocardial stiffness; collagen-dependent and titin-dependent stiffness were increased. These data suggest that the development of HFpEF is dependent on changes in both collagen and titin homeostasis.