Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urotensin II (U-II) is a powerful vasoconstrictor peptide with a potency greater than that of endothelin 1. Its plasma level correlates positively with body weight and is raised in diabetes, renal failure, hypertension, and other cardiovascular diseases, including congestive heart failure and carotid atherosclerosis. Experimental and clinical studies have revealed increased expression of U-II and U-II receptor (UT) in animals with experimentally induced myocardial infarction, heart failure, and in patients with hypertension, atherosclerosis, and diabetes, suggesting a potential role for U-II in coronary artery disease. Peptide and nonpeptide UT ligands have been shown to be effective in antagonizing the effects of U-II in the cardiovascular system. This article aims to review recent advances in physiology and pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases.
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PMID:Role of urotensin II in atherosclerotic cardiovascular diseases. 1860 80

Endothelin (ET)-1 was originally identified in 1988 as a vasoconstrictor peptide produced by vascular endothelial cells. It is now known that ET-1 can be produced by vascular and endocardial endothelium and by myocardial cells. Activation of endothelin receptors modulates a wide variety of biological processes including vascular tone, growth and myocardial contractile function. In mammals, ET-1's effects are mediated through binding to two types of receptors, ET(A) and ET(B). ET(A) receptor activation elicits vasoconstriction, positive inotropism and mitogenesis, and acutely increases myocardial distensibility. ET(B) receptor stimulation generally promotes vasodilatation, mediated by release of nitric oxide and prostacyclins, growth-inhibitory effects and clearance of ET-1 from the circulation. ET(B) receptors can be further subdivided into ET(B1), located in endothelial cells and responsible for vasodilatation and negative inotropic effects, and ET(B2), located in smooth muscle and myocardial cells and responsible for vasoconstriction and positive inotropic effects. Increased levels of cardiac and circulating ET-1 have been linked to development of cardiac dysfunction and severity of heart failure. This has fueled research into the development of endothelin antagonists (ET receptor and converting enzyme inhibitors) in view of the potential benefits that might derive from their use in clinical practice. The present review will focus on current understanding of the mechanisms mediating the myocardial actions of ET-1.
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PMID:Myocardial effects of endothelin-1. 1895 90

The endothelin axis promotes vasoconstriction, suggesting that antagonists of endothelin signaling might be useful in treatment of heart failure. However, promising results from animal trials have not been recapitulated in heart failure patients. Here we review the role of major signaling pathways in the heart that are involved in cell survival initiated by ET-1. These pathways include mitogen-activated protein kinase, phosphatidyl inositol-1,4,5-triphosphate kinase (PI3K-AKT), nuclear factor-kappaB (NF-kappaB), and calcineurin signaling. A better understanding of endothelin-mediated signaling in cardiac cell survival may allow a reevaluation of endothelin receptor antagonists (ETRAs) in the treatment of heart failure.
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PMID:Cardioprotective signaling by endothelin. 1923 51

It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure. Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists, which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123, seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge for developing some combination therapy for the treatment of congestive heart failure.
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PMID:Potential of endothelin-1 and vasopressin antagonists for the treatment of congestive heart failure. 1976 21

The prevalence of cardiovascular disease is lower in middle-aged and older women than men. Increased endothelin-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. It is unknown whether a sex difference in endothelin-1-mediated vasoconstrictor tone exists in middle-aged and older adults. Therefore, we tested the hypothesis that middle-aged and older men would demonstrate greater ET-1-mediated vasoconstrictor tone than age-matched women. Forearm blood flow in response to intra-arterial infusions of endothelin (ET)-1, BQ-123 (a selective ET(A) receptor antagonist), and BQ-788 (a selective ET(B) receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 + or - 1 yr; body mass index: 26.0 + or - 1.0 kg/m(2)) and 25 men (age: 57 + or - 2 yr; body mass index: 26.8 + or - 0.7 kg/m(2)). In response to BQ-123, the increase in forearm blood flow from baseline was significantly higher in the men than the women (24 + or - 5% vs. 9 + or - 5%; P < 0.05). In contrast, the increase in forearm blood flow in response to BQ-123 coinfused with BQ-788 was greater in the women than the men, such that the maximum vasodilation to dual endothelin receptor blockade was similar between men and women (approximately 25%). There was no difference in the vasoconstrictor response to ET-1 between the sexes. These results indicate that middle-aged and older men are under greater ET(A) receptor-mediated vasoconstrictor tone than age-matched women. Since the ET(A) receptor is the predominant receptor subtype in the coronary vasculature, this sex difference in vasoconstrictor tone may be a mechanism contributing to the sex difference in the prevalence of coronary heart disease in middle-aged and older adults.
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PMID:Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. 1993 73

The available data suggest that Urocortin (UCN), a cardioprotective and vasoactive peptide known from fish neuroendocrinology, is involved in cardiac regulation. The aim of this study was to determine UCN plasma concentrations in patients with heart failure (HF). Plasma concentrations of UCN, measured in 42 fully treated HF patients. UCN, were determined using a specific ELISA assay after acidic extraction with Sep-Pak C18 columns. Circulating levels of other neurohormones Nt-proBNP, Nt-proANP and Big ET-1 were also determined. Reference values were obtained from 20 healthy age- and sex-matched subjects. In comparison with controls, UCN plasma concentrations (geometric mean [95% CI]) were significantly increased in HF patients (88 pmol/L [75-105] vs 46 [39-54], p<0.001). As expected, the other neurohormones were also significantly increased in HF patients (Nt-proBNP: 3501 pg/ml [2356-5202] vs 35 [24-51], Nt-proANP: 5498 pg/ml [4336-6971] vs 324 [255-411] and Big ET-1: 15.8 pg/ml [13.6-18.4] vs 5.9 [5.2-6.8]; p<0.01 for all vs controls). No significant correlation was observed between UCN and the other HF biomarkers. Our results demonstrate that plasma concentrations of UCN are significantly increased in patients with HF and that UCN may participate in the neurohumoral response of HF.
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PMID:Circulating levels of stress associated peptide Urocortin in heart failure patients. 1996 89

Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.
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PMID:The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary arterial hypertension: pathogenesis and Endothelin-1 antagonists. 2015 59

Endothelin (ET-1) is the polypeptide about wide spectrum of physiological effects. The results of numerous experimental and clinical investigations showed its essential role also in the pathophysiology of various cardiovascular diseases (arteriosclerosis, heart failure, pulmonary hypertension, renal failure) and some neoplastic conditions. Thus, ET-1 blocking becomes an interesting tool of modern pharmacotherapy, targeted on neurohormonal mechanisms. The article briefly describes biochemical properties of ET-1 and ET and pathophysiological role of ET-1 in selected cardiovascular diseases.
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PMID:[Endothelin in cardiovascular diseases pathophysiology]. 2049 39

Myocardial infarction causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to assist with timely diagnosis, while an increasing number of novel markers have been identified to predict outcome following an acute myocardial infarction or acute coronary syndrome. This may facilitate tailoring of appropriate therapy to high-risk patients. This review focuses on a variety of promising biomarkers which provide diagnostic and prognostic information. Heart-type Fatty Acid Binding Protein and copeptin in combination with cardiac troponin help diagnose myocardial infarction or acute coronary syndrome in the early hours following symptoms. An elevated N-Terminal Pro-B-type Natriuretic Peptide has been well validated to predict death and heart failure following a myocardial infarction. Similarly other biomarkers such as Mid-regional pro-Atrial Natriuretic Peptide, ST2, C-Terminal pro-endothelin 1, Mid-regional pro-Adrenomedullin and copeptin all provide incremental information in predicting death and heart failure. Growth differentiation factor-15 and high-sensitivity C-reactive protein predict death following an acute coronary syndrome. Pregnancy associated plasma protein A levels following chest pain predicts risk of myocardial infarction and revascularisation. Some biomarkers such as myeloperoxidase and high-sensitivity C-reactive protein in an apparently healthy population predicts risk of coronary disease and allows clinicians to initiate early preventative treatment. In addition to biomarkers, various well-validated scoring systems based on clinical characteristics are available to help clinicians predict mortality risk, such as the Thrombolysis In Myocardial Infarction score and Global Registry of Acute Coronary Events score. A multimarker approach incorporating biomarkers and clinical scores will increase the prognostic accuracy. However, it is important to note that only troponin has been used to direct therapeutic intervention and none of the new prognostic biomarkers have been tested and proven to alter outcome of therapeutic intervention. Novel biomarkers have improved prediction of outcome in acute myocardial infarction, but none have been demonstrated to alter the outcome of a particular therapy or management strategy. Randomised trials are urgently needed to address this translational gap before the use of novel biomarkers becomes common practice to facilitate tailored treatment following an acute coronary event.
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PMID:Biomarkers in acute myocardial infarction. 2052 85

Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines (CAs) from secretory vesicles in the adrenal medulla chromaffin cells. Present in the diffuse neuroendocrine system, it has also been detected in rat and human cardiac secretory granules where it co-stores with natriuretic peptide hormones (NPs). Mounting evidence shows that CgA is a marker of cardiovascular dysfunctions (essential hypertension, hypertrophic and dilatative cardiomyopathy, heart failure) and precursor of the cardioactive peptides vasostatin-1 (VS-1) and catestatin (Cts). This review focuses on recent knowledge regarding the myocardial, coronary and anti-adrenergic actions of VS-1. In particular, the negative inotropism, lusitropism and coronary dilation effects of rat CgA1-64 (rCgA) and human recombinant STACgA1-78 (hrSTACgA1-78) are summarized with attention on their counteracting isoproterenol- and endothelin-1-induced positive inotropism, as well as ET-1-dependent coronary constriction. The interactions between vasostatins (VSs), NPs and CA receptors are proposed as a paradigm of the heart capacity to organize complex connection-integration processes for maintaining homeostasis under intense cardio-excitatory stimuli (myocardial stress).
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PMID:The interplay between chromogranin A-derived peptides and cardiac natriuretic peptides in cardioprotection against catecholamine-evoked stress. 2059 92


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