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      Novel biomarkers for cardiovascular risk prediction

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          Abstract

          Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high-sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well validated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.

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          Most cited references142

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          Natriuretic peptides.

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            Galectin-3: an open-ended story.

            Galectins, an ancient lectin family, are characterized by specific binding of beta-galactosides through evolutionary conserved sequence elements of carbohydrate-recognition domain (CRD). A structurally unique member of the family is galectin-3; in addition to the CRD it contains a proline- and glycine-rich N-terminal domain (ND) through which is able to form oligomers. Galectin-3 is widely spread among different types of cells and tissues, found intracellularly in nucleus and cytoplasm or secreted via non-classical pathway outside of cell, thus being found on the cell surface or in the extracellular space. Through specific interactions with a variety of intra- and extracellular proteins galectin-3 affects numerous biological processes and seems to be involved in different physiological and pathophysiological conditions, such as development, immune reactions, and neoplastic transformation and metastasis. The review attempts to summarize the existing information on structural, biochemical and intriguing functional properties of galectin-3.
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              Endothelin

              The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action. Highly selective peptide ETA and ETB antagonists and ETB agonists together with radiolabeled analogs have accurately delineated endothelin pharmacology in humans and animal models, although surprisingly no ETA agonist has been discovered. ET antagonists (bosentan, ambrisentan) have revolutionized the treatment of pulmonary arterial hypertension, with the next generation of antagonists exhibiting improved efficacy (macitentan). Clinical trials continue to explore new applications, particularly in renal failure and for reducing proteinuria in diabetic nephropathy. Translational studies suggest a potential benefit of ETB agonists in chemotherapy and neuroprotection. However, demonstrating clinical efficacy of combined inhibitors of the endothelin converting enzyme and neutral endopeptidase has proved elusive. Over 28 genetic modifications have been made to the ET system in mice through global or cell-specific knockouts, knock ins, or alterations in gene expression of endothelin ligands or their target receptors. These studies have identified key roles for the endothelin isoforms and new therapeutic targets in development, fluid-electrolyte homeostasis, and cardiovascular and neuronal function. For the future, novel pharmacological strategies are emerging via small molecule epigenetic modulators, biologicals such as ETB monoclonal antibodies and the potential of signaling pathway biased agonists and antagonists.
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                Author and article information

                Journal
                J Geriatr Cardiol
                J Geriatr Cardiol
                JGC
                Journal of Geriatric Cardiology : JGC
                Science Press
                1671-5411
                February 2017
                : 14
                : 2
                : 135-150
                Affiliations
                [1 ]Department of Cardiology Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing, China
                [2 ]Department of Radiology, Nanlou Branch of Chinese PLA General Hospital, Beijing, China
                [3 ]Department of Emergency, the Central Hospital of China National Petroleum Corporation, Langfang, Hebei, China
                Author notes
                [*]

                The first two authors contributed equally to this manuscript.

                Correspondence to: Hong-bin LIU, MD & Li-Na HAN MD, Department of Cardiology Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing 100853, China. E-mails: liuhbcad301@ 123456163.com (LIU HB) & hanlina3399111@ 123456sina.com (HAN LN)
                Article
                jgc-14-02-135
                10.11909/j.issn.1671-5411.2017.02.008
                5409355
                28491088
                60459902-9aa4-4854-a558-e9c578d8a8d7
                Institute of Geriatric Cardiology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

                History
                : 9 December 2016
                : 14 February 2017
                : 14 February 2017
                Categories
                Review

                Cardiovascular Medicine
                biomarker,cardiovascular disease,prediction,risk stratification
                Cardiovascular Medicine
                biomarker, cardiovascular disease, prediction, risk stratification

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