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      Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases

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          Abstract

          Arterial stiffness predicts an increased risk of cardiovascular events. Inflammation plays a major role in large arteries stiffening, related to atherosclerosis, arteriosclerosis, endothelial dysfunction, smooth muscle cell migration, vascular calcification, increased activity of metalloproteinases, extracellular matrix degradation, oxidative stress, elastolysis, and degradation of collagen. The present paper reviews main mechanisms explaining the crosstalk between inflammation and arterial stiffness and the most common inflammatory markers associated with increased arterial stiffness, considering the most recent clinical and experimental studies. Diverse studies revealed significant correlations between the severity of arterial stiffness and inflammatory markers, such as white blood cell count, neutrophil/lymphocyte ratio, adhesion molecules, fibrinogen, C-reactive protein, cytokines, microRNAs, and cyclooxygenase-2, in patients with a broad variety of diseases, such as metabolic syndrome, diabetes, coronary heart disease, peripheral arterial disease, malignant and rheumatic disorders, polycystic kidney disease, renal transplant, familial Mediterranean fever, and oral infections, and in women with preeclampsia or after menopause. There is strong evidence that inflammation plays an important and, at least, partly reversible role in the development of arterial stiffness, and inflammatory markers may be useful additional tools in the assessment of the cardiovascular risk in clinical practice. Combined assessment of arterial stiffness and inflammatory markers may improve non-invasive assessment of cardiovascular risk, enabling selection of high-risk patients for prophylactic treatment or more regular medical examination. Development of future destiffening therapies may target pro-inflammatory mechanisms.

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          Most cited references130

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          C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events: An 8-Year Follow-Up of 14 719 Initially Healthy American Women

          The metabolic syndrome describes a high-risk population having 3 or more of the following clinical characteristics: upper-body obesity, hypertriglyceridemia, low HDL, hypertension, and abnormal glucose. All of these attributes, however, are associated with increased levels of C-reactive protein (CRP). We evaluated interrelationships between CRP, the metabolic syndrome, and incident cardiovascular events among 14 719 apparently healthy women who were followed up for an 8-year period for myocardial infarction, stroke, coronary revascularization, or cardiovascular death; 24% of the cohort had the metabolic syndrome at study entry. At baseline, median CRP levels for those with 0, 1, 2, 3, 4, or 5 characteristics of the metabolic syndrome were 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, respectively (P(trend) <0.0001). Over the 8-year follow-up, cardiovascular event-free survival rates based on CRP levels above or below 3.0 mg/L were similar to survival rates based on having 3 or more characteristics of the metabolic syndrome. At all levels of severity of the metabolic syndrome, however, CRP added prognostic information on subsequent risk. For example, among those with the metabolic syndrome at study entry, age-adjusted incidence rates of future cardiovascular events were 3.4 and 5.9 per 1000 person-years of exposure for those with baseline CRP levels less than or greater than 3.0 mg/L, respectively. Additive effects for CRP were also observed for those with 4 or 5 characteristics of the metabolic syndrome. The use of different definitions of the metabolic syndrome had minimal impact on these findings. These prospective data suggest that measurement of CRP adds clinically important prognostic information to the metabolic syndrome.
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            Neutrophil to lymphocyte ratio and cardiovascular diseases: a review.

            The role of inflammatory markers in cardiovascular diseases has been studied extensively and a consistent relationship between various inflammatory markers and cardiovascular diseases has been established in the past. Neutrophil to lymphocyte ratio (NLR) is a new addition to the long list of these inflammatory markers. NLR, which is calculated from complete blood count with differential, is an inexpensive, easy to obtain, widely available marker of inflammation, which can aid in the risk stratification of patients with various cardiovascular diseases in addition to the traditionally used markers. It has been associated with arterial stiffness and high coronary calcium score, which are themselves significant markers of cardiovascular disease. NLR is reported as an independent predictor of outcome in stable coronary artery disease, as well as a predictor of short- and long-term mortality in patients with acute coronary syndromes. It is linked with increased risk of ventricular arrhythmias during percutaneous coronary intervention (PCI) and higher long-term mortality in patients undergoing PCI irrespective of indications of PCI. In patients admitted with advanced heart failure, high NLR was reported with higher inpatient mortality. Recently, NLR has been reported as a prognostic marker for outcome from coronary artery bypass grafting and postcoronary artery bypass grafting atrial fibrillation.
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              Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly

              Vascular remodeling, defined as any enduring change in the size and/or composition of an adult blood vessel, allows adaptation and repair. On the other hand, inappropriate remodeling, including its absence, underlies the pathogenesis of major cardiovascular diseases, such as atherosclerosis and restenosis. Since degradation of the extracellular matrix scaffold enables reshaping of tissue, participation of specialized enzymes called matrix metalloproteinases (MMPs) has become the object of intense recent interest in relation to physiological (“good”) and pathological (“bad”) vascular remodeling. Experimental evidence acquired in vitro and in vivo suggests that the major drivers of vascular remodeling, hemodynamics, injury, inflammation, and oxidative stress, regulate MMP expression and activity. Alternatively, nonspecific MMP inhibition seems to oppose remodeling, as suggested by the inhibition of intimal thickening and outward arterial remodeling. An emerging concept is that MMP-related genetic variations may contribute to heterogeneity in the presentation and natural history of atherosclerosis. The hypothesis that MMPs contribute to weakening of atherosclerotic plaques is especially attractive for the potential development of therapeutic interventions aimed at preventing plaque disruption (“the ugly”), a major cause of acute cardiovascular events. However, the current lack of appropriate experimental tools, including availability of specific MMP inhibitors and pertinent animal models, still limits our understanding of the many actions and relative contributions of specific MMPs. Our future potential ability to control vascular remodeling via regulation of MMPs will also depend on reaching a consensus of what is indeed “good” or “bad” vascular remodeling, concepts that have continued to evolve and change.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/148884
                URI : http://frontiersin.org/people/u/458572
                URI : http://frontiersin.org/people/u/203955
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                31 August 2017
                2017
                : 8
                : 1058
                Affiliations
                [1] 1Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy , Timisoara, Romania
                [2] 2Center for Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy , Timisoara, Romania
                [3] 3Independent Researcher , Vienna, Austria
                [4] 4The Institute of Genetics and Animal Breeding, Polish Academy of Sciences , Jastrzębiec, Poland
                [5] 5Department of Microscopic Morphology, “Victor Babes” University of Medicine and Pharmacy , Timisoara, Romania
                [6] 62nd Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy , Timisoara, Romania
                [7] 7Department of Cardiology, “Victor Babes” University of Medicine and Pharmacy , Timisoara, Romania
                [8] 8Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna , Vienna, Austria
                [9] 9Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna , Vienna, Austria
                Author notes

                Edited by: Jixin Zhong, Case Western Reserve University, United States

                Reviewed by: Xuhui Feng, Indiana University System, United States; Ding Xinchun, Indiana University, Purdue University Indianapolis, United States; Xiaojing Yue, La Jolla Institute for Allergy and Immunology, United States

                *Correspondence: Ioana Mozos, ioana_mozos@ 123456yahoo.com ; Atanas G. Atanasov, a.atanasov.mailbox@ 123456gmail.com

                Specialty section: This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2017.01058
                5583158
                28149297
                258ee756-fb0a-4f9b-80e3-4f1a9b7434de
                Copyright © 2017 Mozos, Malainer, Horbańczuk, Gug, Stoian, Luca and Atanasov.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 June 2017
                : 15 August 2017
                Page count
                Figures: 1, Tables: 6, Equations: 0, References: 161, Pages: 16, Words: 14281
                Funding
                Funded by: Krajowy Naukowy Osrodek Wiodacy 10.13039/501100008648
                Award ID: 05-1/KNOW2/2015
                Categories
                Immunology
                Review

                Immunology
                inflammatory markers,arterial stiffness,inflammation,cardiovascular diseases,cardiovascular risk factors

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