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      Serum Endothelin-1 Correlates with Myocardial Injury and Independently Predicts Adverse Cardiac Events in Non-ST-Elevation Acute Myocardial Infarction

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          Abstract

          Introduction

          Serum endothelin-1 is increasingly released in acute myocardial infarction, by necrotic cardiomyocytes. In non-ST-elevation acute myocardial infarction (Non-STEMI), increased serum endothelin-1 on-admission may have clinical significance during acute hospitalisation events.

          Objective

          The purpose of this study is to investigate whether increased serum endothelin-1 level predict adverse cardiac events in patients hospitalized with Non-STEMI.

          Methods

          The design of this research was a prospective cohort study. Consecutive subjects with Non-STEMI undergoing symptom onset ≤24 hour were enrolled and observed during intensive hospitalization. Serum endothelin-1, troponin-I, and hs-C reactive protein were measured from peripheral blood taken on-admission. In-hospital adverse cardiac events were a composite of death, acute heart failure, cardiogenic shock, reinfarction, and resuscitated VT/VF.

          Results

          We enrolled 66 subjects. The incidence of in-hospital adverse cardiac events is 13.6% (10 out of 66 subjects). Serum endothelin-1 level was significantly higher in subjects with in-hospital adverse cardiac events. Subjects with endothelin-1 level >2.59 pg/mL independently predicted adverse cardiac events in hospitalised Non-STEMI patients (adjusted odds ratio 44.43, 95% confidence interval: 1.44-1372.99, p value 0.03). The serum endothelin-1 level was correlated with serum troponin I level (correlation coefficient of 0.413, p value 0.012).

          Conclusion

          Increased serum endothelin-1 on-admission correlated with increased troponin-I and independently predicted in-hospital adverse cardiac events in patients with Non-STEMI.

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          Most cited references16

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          Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs.

          The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, ET-3, and ET-4. It exerts various biological effects, including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. ET-1 is synthesized by endothelin-converting enzymes (ECE), chymases, and non-ECE metalloproteases; it is regulated in an autocrine fashion in vascular and nonvascular cells. ET-1 acts through the activation of G(i)-protein-coupled receptors. ET(A) receptors mediate vasoconstriction and cell proliferation, whereas ET(B) receptors are important for the clearance of ET-1, endothelial cell survival, the release of nitric oxide and prostacyclin, and the inhibition of ECE-1. ET is activated in hypertension, atherosclerosis, restenosis, heart failure, idiopathic cardiomyopathy, and renal failure. Tissue concentrations more reliably reflect the activation of the ET system because increased vascular ET-1 levels occur in the absence of changes in plasma. Experimental studies using molecular and pharmacological inhibition of the ET system and the first clinical trials have demonstrated that ET-1 takes part in normal cardiovascular homeostasis. Thus, ET-1 plays a major role in the functional and structural changes observed in arterial and pulmonary hypertension, glomerulosclerosis, atherosclerosis, and heart failure, mainly through pressure-independent mechanisms. ET antagonists are promising new agents in the treatment of cardiovascular diseases.
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            Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries.

            Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01). ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.
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              Increased plasma endothelin-1 in the early hours of acute myocardial infarction.

              Endothelin is a novel endothelium-derived vasoactive peptide with potent vasoconstrictor action in the coronary bed; however, its possible contribution to myocardial ischemia and infarction is not known. Plasma endothelin-1 concentration was measured with use of a radioimmunoassay in serial venous samples from 22 patients over a 72 h period after acute myocardial infarction (14 patients with uncomplicated infarction [group I] and 8 patients with hemodynamic or ischemic sequelae [group II]). Twenty-two normal subjects and seven patients with stable angina served as the control subjects. Endothelin-1 levels in patients with stable coronary disease were not different from those of normal subjects (0.62 +/- 0.56 and 0.76 +/- 0.38 pg/ml, respectively). In group I, plasma levels of endothelin-1 rose sharply after myocardial infarction, reaching a peak of 4.95 +/- 0.78 pg/ml at 6 h after the onset of chest pain (p less than 0.05 compared with values in control subjects) and returning rapidly toward the normal range by 24 h. Patients with complicated infarction (group II) demonstrated a similar rapid increase in plasma endothelin-1 to a peak value of 8.29 +/- 1.95 pg/ml; however, plasma endothelin-1 remained elevated in these patients, becoming significantly different from values in group I at 48 and 72 h. There was no correlation between peak increases in creatine kinase and peak endothelin-1 in either group, suggesting that the stimulus for elevation of endothelin-1 was not myocardial necrosis itself. Furthermore, left ventricular ejection fraction did not correlate with the increase in endothelin-1 in group I patients, whereas there was a significant inverse relation between ventricular function and plasma endothelin-1 in group II.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                Journal
                Int J Vasc Med
                Int J Vasc Med
                IJVM
                International Journal of Vascular Medicine
                Hindawi
                2090-2824
                2090-2832
                2020
                4 August 2020
                : 2020
                : 9260812
                Affiliations
                1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada-Dr. Sardjito Hospital, Yogyakarta, Indonesia
                2Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada-Dr. Sardjito Hospital, Yogyakarta, Indonesia
                Author notes

                Academic Editor: Alberto Caggiati

                Author information
                https://orcid.org/0000-0002-6373-1033
                Article
                10.1155/2020/9260812
                7424398
                fef0e568-11f9-4140-b960-9e637c149ea8
                Copyright © 2020 Anggoro Budi Hartopo et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 April 2020
                : 19 July 2020
                : 23 July 2020
                Funding
                Funded by: Dana Masyarakat Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada Yogyakarta Indonesia
                Categories
                Research Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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