Rutkovskiy Arkady, Sagave Julia, Czibik Gabor, Baysa Anton, Zihlavnikova Enayati Katarina, Hillestad Vigdis, Dahl Christen Peder, Fiane Arnt, Gullestad Lars, Gravning Jørgen, Ahmed Shakil, Attramadal Håvard, Valen Guro, Vaage Jarle
a Division of Physiology, Department of Molecular Medicine , Institute of Basic Medical Sciences, University of Oslo , Oslo , Norway.
b International Laboratory of Bioinformatics and Genomics, ITMO University , Saint-Petersburg , Russia.
Scand J Clin Lab Invest. 2017 Sep;77(5):321-331. doi: 10.1080/00365513.2017.1318447. Epub 2017 May 2.
We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.
我们旨在研究骨形态发生蛋白2、其受体1b以及结缔组织生长因子在心脏中的表达情况，这些因子与心脏胚胎发育有关，研究对象包括经历缺血/缺氧、心力衰竭的人类和小鼠，以及正在进行心脏重塑的人类和小鼠。将因扩张型心肌病或冠状动脉疾病导致终末期心力衰竭患者的左心室活检样本，与供体心脏以及心脏功能正常且正在接受冠状动脉搭桥手术患者的活检样本进行比较。通过永久性结扎左冠状动脉建立心肌梗死后重塑的小鼠模型。在24小时、2周和4周后，通过实时聚合酶链反应和蛋白质免疫印迹法对心脏进行分析。扩张型心肌病患者和心肌梗死后的小鼠，其心脏中结缔组织生长因子的表达增加。因冠状动脉疾病导致心力衰竭的人类心脏以及心肌梗死后的小鼠心脏中，骨形态发生蛋白2增加。心力衰竭患者心脏中骨形态发生蛋白受体1β的基因表达降低，但在小鼠永久性结扎左冠状动脉两周后增加。总之，扩张型心肌病患者心脏中结缔组织生长因子上调，心肌梗死导致心脏重塑过程中骨形态发生蛋白2上调，而人类衰竭心脏中其受体1b下调。一种可能的解释或许是机体试图启动再生过程，这有待进一步的机制研究加以探讨。
