Stein B, Eschenhagen T, Rüdiger J, Scholz H, Förstermann U, Gath I
Institüt für Experimentelle und Klinische Pharmakologie ünd Toxikologie, Abteilung Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany.
J Am Coll Cardiol. 1998 Nov;32(5):1179-86. doi: 10.1016/s0735-1097(98)00399-4.
The purpose of the present study was to examine the expression of the endothelial-type nitric oxide synthase (NOS III) and the inducible-type NOS (NOS II) in human myocardium and their regulation in heart failure from patients with different etiologies.
In heart failure, plasma levels of nitrates were found to be elevated. However, data on myocardial NOS expression in heart failure are conflicting.
Using RNase protection analysis and Western blotting, the expression of NOS III and NOS II was investigated in ventricular myocardium from nonfailing (NF) hearts (n=5) and from failing hearts of patients with idiopathic dilated cardiomyopathy (dCMP, n=14), ischemic cardiomyopathy (iCMP, n=9) or postmyocarditis cardiomyopathy (mCMP, n=7). Furthermore, immunohistochemical studies were performed to localize NOS III and NOS II within the ventricular myocardium.
In failing human hearts, NOS III mRNA levels were increased to 180% in dCMP, 200% in iCMP and to 210% in mCMP as compared to NF hearts. Similarly, in Western blots (using constitutively expressed beta-tubulin as a reference) NOS III protein expression was increased about twofold in failing compared to NF hearts. Immunohistochemical studies with a selective antibody to NOS III showed no obvious differences in the staining of the endothelium of cardiac blood vessels from NF and failing human hearts. However, NOS III-immunoreactivity in cardiomyocytes was significantly more intense in failing compared to NF hearts. Low expression of NOS II mRNA was detected in only 2 of 30 failing human hearts and was not found in NF hearts. Inducible-type NOS protein was undetectable in either group.
We conclude that the increased NOS III expression in the ventricular myocardium of failing human hearts may contribute to the contractile dysfunction observed in heart failure and/or may play a role in morphologic alterations such as hypertrophy and apoptosis of cardiomyocytes.
本研究旨在检测人心肌中内皮型一氧化氮合酶（NOS III）和诱导型一氧化氮合酶（NOS II）的表达情况，以及它们在不同病因心力衰竭患者中的调控机制。
在心力衰竭患者中，血浆硝酸盐水平升高。然而，关于心力衰竭时心肌中一氧化氮合酶表达的数据存在矛盾。
采用核糖核酸酶保护分析和蛋白质免疫印迹法，研究了非衰竭（NF）心脏（n = 5）以及特发性扩张型心肌病（dCMP，n = 14）、缺血性心肌病（iCMP，n = 9）或心肌炎后心肌病（mCMP，n = 7）患者衰竭心脏心室肌中NOS III和NOS II的表达。此外，还进行了免疫组织化学研究，以确定心室肌中NOS III和NOS II的定位。
与NF心脏相比，在衰竭的人心脏中，dCMP中NOS III mRNA水平增加到180%，iCMP中增加到200%，mCMP中增加到210%。同样，在蛋白质免疫印迹中（以组成性表达的β-微管蛋白作为参照），与NF心脏相比，衰竭心脏中NOS III蛋白表达增加了约两倍。用针对NOS III的选择性抗体进行的免疫组织化学研究显示，NF心脏和衰竭人心脏的心腔血管内皮染色无明显差异。然而，与NF心脏相比，衰竭心脏中心肌细胞的NOS III免疫反应性明显更强。在30例衰竭人心脏中，仅2例检测到低水平的NOS II mRNA表达，而NF心脏中未检测到。两组中均未检测到诱导型一氧化氮合酶蛋白。
我们得出结论，衰竭人心脏心室肌中NOS III表达增加可能导致心力衰竭时观察到的收缩功能障碍，和/或可能在心肌细胞肥大和凋亡等形态学改变中起作用。
