Kozłowska Bogna, Sochanowicz Barbara, Kraj Leszek, Palusińska Małgorzata, Kołsut Piotr, Szymański Łukasz, Lewicki Sławomir, Śmigielski Witold, Kruszewski Marcin, Leszek Przemysław
Department of Heart Failure and Transplantology, The Cardinal Stefan Wyszyński National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland.
Centre of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa, Poland.
J Clin Med. 2022 Feb 5;11(3):837. doi: 10.3390/jcm11030837.
In heart failure, iron deficiency is a common comorbid disease that negatively influences exercise tolerance, number of hospitalizations and mortality rate, and this is why iron iv supplementation is recommended. Little is known about the changes in iron-related proteins in the human HF myocardium. The purpose of this study was to assess iron-related proteins in non-failing (NFH) vs. failing (FH) human myocardium. The study group consisted of 58 explanted FHs; control consisted of 31 NFHs unsuitable for transplantation. Myocardial proteins expressions: divalent metal transporter (DMT-1); L-type calcium channel (L-CH); transferrin receptors (TfR-1/TfR-2); ferritins: heavy (FT-H) or light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN), regulatory factors and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH, the expression in almost all proteins responsible for iron transport: DMT-1, TfR-1, L-CH, except TfR-2, and storage: FT-H/-L/-MT were reduced, with no changes in FPN. Moreover, 4-HNE expression (pg/mg; NFH 10.6 ± 8.4 vs. FH 55.7 ± 33.7; < 0.0001) in FH was increased. HNE-4 significantly correlated with DMT-1 (r = -0.377, = 0.036), L-CH (r = -0.571, = 0.001), FT-H (r = -0.379, = 0.036), also FPN (r = 0.422, = 0.018). Reducing iron-gathering proteins and elevated oxidative stress in failing hearts is very unfavorable for myocardiocytes. It should be taken into consideration before treatment with drugs or supplements that elevate free oxygen radicals in the heart.
在心力衰竭中，缺铁是一种常见的合并症，会对运动耐量、住院次数和死亡率产生负面影响，这就是推荐静脉补充铁剂的原因。关于人类心力衰竭心肌中铁相关蛋白的变化，我们知之甚少。本研究的目的是评估非衰竭（NFH）与衰竭（FH）人类心肌中的铁相关蛋白。研究组由58例移植的FH患者组成；对照组由31例不适宜移植的NFH患者组成。检测心肌蛋白表达：二价金属转运体（DMT-1）；L型钙通道（L-CH）；转铁蛋白受体（TfR-1/TfR-2）；铁蛋白：重链（FT-H）或轻链（FT-L）、线粒体铁蛋白（FT-MT）；铁转运蛋白（FPN）、调节因子和氧化应激标志物：4-羟基壬烯醛（4-HNE）。在FH中，几乎所有负责铁转运的蛋白（DMT-1、TfR-1、L-CH，TfR-2除外）和储存蛋白（FT-H/-L/-MT）的表达均降低，而FPN无变化。此外，FH中4-HNE的表达（pg/mg；NFH为10.6±8.4，FH为55.7±33.7；P<0.0001）增加。4-HNE与DMT-1（r = -0.377，P = 0.036）、L-CH（r = -0.571，P = 0.001）、FT-H（r = -0.379，P = 0.036）以及FPN（r = 0.422，P = 0.018）显著相关。心力衰竭时铁聚集蛋白减少和氧化应激升高对心肌细胞非常不利。在用可升高心脏中游离氧自由基的药物或补充剂治疗之前，应予以考虑。
