endothelin-1 and Angina--Unstable

The pathophysiologic meaning of elevated circulating endothelin-1 (ET-1) levels in various cardiovascular diseases is not understood. The aim of this study was to measure ET-1 and big ET-1 levels in patients with unstable angina pectoris (UAP) and within 5 days after stabilization. These values were compared to those of patients with stable angina pectoris (SAP) and to healthy controls (Co). In addition, a venous occlusion test was performed as an endothelial provocation test to characterize endothelial function. Big ET-1 levels were increased to 2.6 +/- 1.5 fmol/ml during unstable angina pectoris compared to normal values of 0.52 +/- 0.07 fmol/ml (p < 0.03; n = 14). After stabilization, big ET-1 decreased to 1.5 +/- 0.4 fmol/ml within 5 days (n.s.). ET-1 levels were not increased during UAP and after stabilization. ET-1 and big ET-1 levels from patients with SAP did not differ from those of healthy controls. The venous occlusion test resulted in an increase of ET-1 levels (0.3 +/- 0.02 to 0.46 +/- 0.02 fmol/mg, p = 0.008; SAP 0.3 +/- 0.04 to 0.39 +/- 0.05 fmol/ml, p = 0.009) in healthy controls and in patients with SAP. In contrast, patients with UAP showed no significant increase in ET-1 with this test. After stabilization for 5 days, the provocation test induced an increase in circulating ET-1 in patients with UAP comparable to that of controls (0.62 +/- 0.18 fmol/mg vs. 0.95 +/- 0.25 fmol/mg; p < 0.02). In summary, during UAP big ET-1 values are significantly increased and ET-1 values tend to be elevated. In an endothelial provocation test, ET-1 values did not increase. This might reflect a general activation of the endothelium in UAP during the acute stage, because the normal response is recovered 5 days later.

Topics: Adult; Angina Pectoris; Angina, Unstable; Endothelin-1; Endothelins; Humans; Protein Precursors; Reference Values

Topics: Adult; Angina, Unstable; Coronary Artery Disease; Endothelial Cells; Endothelin-1; Humans; Myocardial Infarction; Peptides; Plasma; Tissue Plasminogen Activator; von Willebrand Factor

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

This study was aimed to assess the diagnostic value of laboratory markers of endothelial lesions in patients with unstable angina (UA). Plasma levels of CRP, homocysteine, endothelin-1 (ET1), and pregnancy-associated plasma protein (pAPP-A) were measured by an ultrasensitive method in 51 patients. They were followed up for 4 months to evaluate the clinical picture of CHD and dynamics of laboratory parameters. The hospitalized patients with UA had elevated baseline levels of CRP (5.02+-3.35 mg/ml) during the entire study period. PAPP-A and homocysteine levels were significantly decreased (p<0.05 and p<0.0 respectively). Patients with deteriorated clinical picture of CHD had significantly elevated ET1 levels (p<0.05) both on day 1 and 4 months later It is concluded that ET1 levels increase in patients with UA and severe prognostically unfavourable CHD.

Topics: Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Endothelin-1; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Risk Factors; Severity of Illness Index; Statistics as Topic; Time Factors

Patients with the worse clinical picture of ischemic heart disease were found to have a significantly high concentration of endothelin-1 (p < 0.05) both within 24 hours of observation and within 4 months after. The baseline level of C-reactive protein was significantly high (p < 0.05) throughout the study. The plasma level of the protein associated with pregnancy (p < 0.05) and homocysteine (p < 0.01) were significantly reduced.

Topics: Angina, Unstable; Biomarkers; C-Reactive Protein; Endothelin-1; Endothelium, Vascular; Homocysteine; Humans; Pregnancy-Associated Plasma Protein-A

Ischemic preconditioning may provide a systemic organ protection, evident as the phenomenon known as remote preconditioning. Unstable angina may be a clinical analogue to ischemic preconditioning. Vein graft harvesting induces inflammation of the graft wall. We hypothesized that preoperative unstable angina preconditions vein grafts and reduces the inflammatory response to graft harvesting. Consecutive patients with stable or unstable angina undergoing open heart surgery (n = 12 in each group) were studied. Saphenous vein biopsies were collected at the start of graft harvesting, and when the last proximal anastomosis to the aorta was finished (average 112 minutes later). Gene expression of inflammatory mediators (tumor necrosis factor alpha, interleukin-1beta (IL-1beta), E-selectin (CD62E), intercellular leukocyte adhesion molecule 1, inducible nitric oxide synthase, endothelin-1) increased after surgical handling (semiquantitative RT-PCR). In vein grafts from unstable patients the increase was attenuated for Il-1beta (p < 0.004) and CD62E (p < 0.001). In stable patients the protein expression of IkappaBalpha and heat shock protein72 was reduced by surgical handling (p < 0.04), but was not influenced in unstable patients (immunoblotting). In vitro relaxation to acetylcholine was enhanced, and contractions to phenylephrine and endothelin-1 were attenuated in veins rings from unstable patients (p < 0.003). In conclusion, surgical handling of vein grafts induces inflammation of the vessel wall. This response was reduced in grafts from patients with unstable angina, indicating a possible systemic preconditioning-like effect of acute coronary syndromes.

Topics: Aged; Angina Pectoris; Angina, Unstable; Cell Adhesion Molecules; E-Selectin; Endothelin-1; Female; Gene Expression; Gene Expression Regulation; HSP72 Heat-Shock Proteins; Humans; I-kappa B Proteins; Inflammation; Interleukin-1beta; Ischemic Preconditioning; Male; Middle Aged; Nitric Oxide Synthase; Reverse Transcriptase Polymerase Chain Reaction; Saphenous Vein; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Resistin, a novel adipokine linked to insulin resistance and obesity in rodents, which is derived mainly from macrophages and identified in atheromas in human, has been shown to play a potential role in atherosclerosis. Resistin levels were reported to increase in coronary artery disease (CAD), while data concerning resistin in different stages of CAD in Chinese people are lacking. The aim of this study was to assess whether plasma concentrations of resistin differed between patients with unstable and stable angina pectoris.. Plasma resistin levels were determined by means of enzyme-linked immunosorbent assay (ELISA) in 46 patients with unstable angina (UAP), 37 with stable angina (SAP) and 31 control subjects.. Plasma concentrations of resistin were significantly increased in UAP group (geometric mean (interquartile range) 12.09 ng/ml (8.40, 18.08)) in comparison with SAP (9.04 ng/ml (7.09, 11.44)) and control groups (8.71 ng/ml (6.58, 11.56)). No differences in resistin levels were found between patients with SAP and controls. We also found that plasma resistin positively correlated with leukocyte counts (r = 0.21, P = 0.027), high sensitive C-reactive protein (hs-CRP) (r = 0.25, P = 0.008), and endothelin-1 (r = 0.21, P = 0.025) after adjustment for age, sex and BMI.. Resistin may be involved in the development of CAD by influencing systemic inflammation and endothelial activation.

Topics: Aged; Angina, Unstable; Body Mass Index; C-Reactive Protein; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Resistin

In this study we assessed whether serum endothelin-1 levels were associated with indexes of disease severity in unstable angina, including troponin I, C-reactive protein, and transient myocardial ischemia. Endothelin-1 levels were higher in patients who had transient myocardial ischemia and in those who had 3-vessel disease on angiography but were not significantly correlated with levels of C-reactive protein and troponin I.

Topics: Aged; Angina, Unstable; Biomarkers; C-Reactive Protein; Electrocardiography, Ambulatory; Endothelin-1; Female; Humans; Male; Myocardial Ischemia; Prospective Studies; Severity of Illness Index; Troponin

It has been documented that an elevated endothelin-1 (ET-1) plasma concentration is associated with an increased risk of serious coronary events and the presence of angiographically documented coronary artery disease (CAD). The results of a few studies which examined ET-1 plasma level in patients with stable or unstable angina, were inconclusive.. To assess whether ET-1 blood concentration measured in the coronary sinus and peripheral vein is associated with clinical symptoms in patients with multi-vessel CAD.. The study group consisted of 23 patients with multi-vessel CAD of whom 11 had unstable angina and 12 - stable angina. Both groups were matched with regard to age, gender and the presence of cardio-vascular risk factors. Blood samples for ET-1 assessment were taken during coronary angiography simultaneously from the coronary sinus and femoral vein. ET-1 was measured using an immunoenzymatic method.. ET-1 plasma level in the peripheral venous circulation was similar in patients with unstable or stable angina (0.45+/-0.18 pmol/L versus 0.46+/-0.14 pmol/L, NS) whereas ET-1 level in the coronary sinus was significantly higher in patients with unstable angina (1.44+/-0.47 pmol/L versus 0.34+/-0.17 pmol/L, p<0.05).. ET-1 concentration in the coronary sinus is significantly higher in patients with unstable rather than stable angina which confirms the role of ET-1 in the pathogenesis of CAD. Our results suggest a possible future role of endothelin receptor blockers in the treatment of patients with unstable angina.

Topics: Angina, Unstable; Coronary Angiography; Endothelin-1; Female; Humans; Male; Middle Aged

The aim of this study was to determine the plasma and pericardial levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big ET-1) in patients with unstable and stable angina prior to and following coronary bypass surgery. To further investigate the content of ET-1, tissue levels were studied in the internal mammary artery (IMA) in patients with stable and unstable angina pectoris. Finally, the difference in reactivity of the IMA to ET-1 and Big ET-1 in stable and unstable patients was evaluated.. Plasma and pericardial levels of ET-1 and Big ET-1 were determined with radioimmunoassay in 81 patients (33 unstable) immediately before coronary bypass surgery, and at 6, 14, 40 and 64 h following the procedure. Specimens of the distal IMA from 12 patients (six unstable) were collected at the beginning of surgery for determination of tissue levels of ET-1. Additionally, distal internal mammary arteries were obtained from another 24 patients (12 unstable). These vessels were mounted in organ baths for functional studies on vascular reactivity to ET-1 and Big ET-1.. The peripheral plasma levels of ET-1 in unstable patients were significantly lower in patients with unstable angina compared with patients with stable angina pectoris at all points of measurement. The levels of Big ET-1 were significantly higher pre-operatively in the unstable group, but decreased to similar levels to those of stable patients following coronary bypass grafting. There was no difference in ET-1 tissue content in the IMA between the patients. ET-1 and Big ET-1 caused an endothelin(A) (ET(A))-receptor blocker sensitive, concentration-dependent contraction of the IMA obtained from stable as well as unstable patients.. It is concluded that unstable angina pectoris is associated with an increased ET-1 turnover. This increased turnover may participate in the local regulation of coronary vascular tone with subsequent influence of the condition of the patients. The present investigation also implies that ET(A)-blockade may be useful as an additional pharmacological principal in the treatment of unstable angina pectoris prior to revascularization, as well as to prevent post-operative arterial graft spasm.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Biomarkers; Coronary Artery Bypass; Endothelin-1; Endothelins; Female; Follow-Up Studies; Humans; Male; Mammary Arteries; Middle Aged; Myocardium; Postoperative Period; Preoperative Care; Probability; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Statistics, Nonparametric; Treatment Outcome

An elevated plasma level of endothelin-1 was reported in several cardiovascular conditions including unstable angina pectoris and myocardial infarction. The present study was designed to evaluate the time course of the endothelin-1 release in unstable angina pectoris and to assess its relationship to the development of myocardial infarction and coronary vessel occlusion. The cohort studied included 32 patients with the clinical diagnosis of unstable angina pectoris who had been admitted to the coronary care unit and subsequently underwent coronary angiography (group A). Fourteen patients with chronic stable angina pectoris referred to routine diagnostic coronary angiography served as the control group (group B). A significant difference in the endothelin-1 plasma level was found between both groups, the values being 10.2 +/- 5.3 and 6.0 +/- 3.1 pg/ml (p < 0.01), respectively. There were, however, no significant differences between the following subdivisions of group A: patients with and without subsequent myocardial infarction; those with angiographically documented occlusion of at least one major branch of the coronary artery and no occlusion; and finally, those with persisting symptoms of angina pectoris and with favorable response to treatment. Neither was there any difference found among the subgroups differing in the time interval between the onset of chest pain and blood sampling. The time course of endothelin plasma concentrations showed elevated values lasting for more than 96 h after the index episode of prolonged chest pain. No correlation with the subsequent clinical course could be inferred. Thus, plasma endothelin level was elevated in patients with unstable angina pectoris and myocardial infarction and the increase persisted for several days after the onset of symptoms.

Topics: Adult; Aged; Angina, Unstable; Biomarkers; Coronary Angiography; Endothelin-1; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Reference Values; Sensitivity and Specificity; Time Factors

The role of endogenous endothelin-1 in variant angina was investigated using two endothelin receptor antagonists: LU 135252 (ET(A)) and BQ 788 (ET(B)). Cyclic flow reductions were induced in a coronary artery of mongrel dogs by combining critical stenosis with endothelial injury. One hour after induction of cyclic coronary flow reductions the dogs were randomized to intravenous treatment with either saline, or LU 135252 (10 mg kg(-1)), or BQ 788 (0.1 mg kg(-1)). Cyclic coronary flow reductions were monitored for two hours after drug and remained constant in controls as well as after BQ 788. LU 135252 reduced the number of cyclic coronary flow reductions significantly (about 50%) without effects on hemodynamics or hemostasis.

Topics: Angina, Unstable; Animals; Coronary Circulation; Coronary Vessels; Dogs; Endothelin Receptor Antagonists; Endothelin-1; Endothelium, Vascular; Oligopeptides; Phenylpropionates; Piperidines; Pyrimidines; Receptor, Endothelin B; Receptors, Endothelin

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.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Coronary Disease; Endothelin-1; Endothelin-2; Endothelins; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Protein Precursors; Radioimmunoassay; Reference Values; Risk Factors