Borries M, Heins M, Fischer Y, Stiegler H, Schoebel F C, Reinauer H, Strauer B E, Leschke M
Klinik für Kardiologie, Pneumologie und Angiologie, Heinrich-Heine-Universität, Düsseldorf.
Z Kardiol. 1996 Oct;85(10):761-7.
Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic potency, is generated from its precursor big-endothelin (BET) in a proteolytic process and discussed as a pathogenetic factor in coronary artery disease and in the acute coronary syndromes. Several studies documented elevated plasma endothelin concentrations in acute myocardial infarction, but conflicting results were reported in patients with stable and unstable angina. Only few studies determined big endothelin, although it half-life and plasma concentrations are higher in comparison to endothelin. ET and BET levels (Radioimmunoassay, Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n = 20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum-maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1); BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1-1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p < 0.001). Also, the concentrations of the peptides differed significantly dependent on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p < 0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET concentrations before the increase of creatinecinase. There was no correlation between number of risk factors per patient, cholesterin and subfractions, severity of CAD classified in one-two-three-vessel disease or coronary score according to modified criteria of the American Heart Association (AHA). We conclude that in patients with coronary artery disease endothelin and big endothelin levels are elevated and related to the clinical and not to the morphological severity of coronary artery disease. Big endothelin is the more sensitive parameter in comparison to endothelin and indicates a severe course of myocardial ischemia in patients with unstable angina. The development of assays with the possibility of a quick determination of the peptides may be valuable for risk stratification of acute coronary events.
内皮素（ET）是最强大的内源性血管收缩剂，具有促有丝分裂活性，它在蛋白水解过程中由其前体大内皮素（BET）生成，并被认为是冠状动脉疾病和急性冠状动脉综合征的发病因素。多项研究记录了急性心肌梗死患者血浆内皮素浓度升高，但关于稳定型和不稳定型心绞痛患者的研究结果却相互矛盾。虽然大内皮素的半衰期和血浆浓度比内皮素更高，但仅有少数研究测定过大内皮素。我们测定了稳定型心绞痛患者（SAP，n = 20）、不稳定型心绞痛患者（IAP，n = 12）、急性心肌梗死患者（AMI，n = 12）和健康受试者（NP，n = 11）的ET和BET水平（放射免疫分析法，维也纳Biomedica GmbH公司）。稳定型心绞痛患者（SAP：ET 0.7（0.3 - 1.1）；BET 1.7（0.7 - 2.9））、不稳定型心绞痛患者（IAP：ET 1.0（0.5 - 1.7）；BET 2.5（1.3 - 4.1））和急性心肌梗死患者（AMI：ET 1.2（0.6 - 2.3）；BET 3.6（3.2 - 5.3））的ET和BET浓度（fmol/ml为单位的中位数（最小值 - 最大值））与对照组（NP：ET 0.5（0.4 - 0.7）；BET 1.4（1.1 - 1.7））相比有显著差异（SAP与NP比较：ET p < 0.01；BET p < 0.05；IAP和AMI与NP比较：ET和BET p < 0.001）。此外，肽类浓度因冠状动脉疾病的临床严重程度不同而有显著差异（AMI与SAP比较：ET和BET p < 0.001；AMI与IAP比较：BET p < 0.05；IAP与SAP比较：ET p < 0.05；BET p < 0.01）。15名大内皮素浓度超过3 fmol/ml的患者中有12名发生了急性心肌梗死。12名AMI患者中有7名在肌酸激酶升高之前ET和BET浓度就已升高。每位患者的危险因素数量、胆固醇及其亚组分、根据美国心脏协会（AHA）修改标准分类的一 - 二 - 三支血管病变或冠状动脉评分的CAD严重程度之间均无相关性。我们得出结论，在冠状动脉疾病患者中，内皮素和大内皮素水平升高，且与冠状动脉疾病的临床严重程度相关，而非形态学严重程度相关。与内皮素相比，大内皮素是更敏感的参数，提示不稳定型心绞痛患者心肌缺血病情严重。开发能够快速测定这些肽类的检测方法可能对急性冠状动脉事件的风险分层有重要价值。
