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      Correlation between Inflammatory Markers of Atherosclerosis and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

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          Abstract

          Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.

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          Atherosclerosis. the road ahead.

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            Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.

            A study in vitro of specimens of human aortic and common carotid arteries was carried out to determine the feasibility of direct measurement (i.e., not from residual lumen) of arterial wall thickness with B mode real-time imaging. Measurements in vivo by the same technique were also obtained from common carotid arteries of 10 young normal male subjects. Aortic samples were classified as class A (relatively normal) or class B (with one or more atherosclerotic plaques). In all class A and 85% of class B arterial samples a characteristic B mode image composed of two parallel echogenic lines separated by a hypoechoic space was found. The distance between the two lines (B mode image of intimal + medial thickness) was measured and correlated with the thickness of different combinations of tunicae evaluated by gross and microscopic examination. On the basis of these findings and the results of dissection experiments on the intima and adventitia we concluded that results of B mode imaging of intimal + medial thickness did not differ significantly from the intimal + medial thickness measured on pathologic examination. With respect to the accuracy of measurements obtained by B mode imaging as compared with pathologic findings, we found an error of less than 20% for measurements in 77% of normal and pathologic aortic walls. In addition, no significant difference was found between B mode-determined intimal + medial thickness in the common carotid arteries evaluated in vitro and that determined by this method in vivo in young subjects, indicating that B mode imaging represents a useful approach for the measurement of intimal + medial thickness of human arteries in vivo.
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              Direct proinflammatory effect of C-reactive protein on human endothelial cells.

              The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known. We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. Incubation with recombinant human CRP (10 microg/mL) for 24 hours induced an approximately 10-fold increase in expression of ICAM-1 and a significant expression of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1beta. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 microg/mL and reached a maximum at 50 microg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1beta was able to induce adhesion molecule expression in the absence of human serum. CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                29 January 2014
                February 2014
                : 19
                : 2
                : 1651-1662
                Affiliations
                [1 ]Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari 70124, Italy; E-Mails: piero.sc@ 123456hotmail.it (P.S.); annapaolazito@ 123456yahoo.it (A.Z.); francescacortese@ 123456hotmail.it (F.C.).
                [2 ]Institute of Respiratory Disease, University of Bari, Bari 70124, Italy; E-Mails: b.boninfante@ 123456alice.it (B.B.); iposoli9@ 123456gmail.com (V.A.F.); vitaliano40@ 123456libero.it (V.N.Q.); valevent@ 123456libero.it (V.A.V.); mariodmn84@ 123456hotmail.com (M.F.D.); onofrio.resta@ 123456uniba.it (O.R.).
                [3 ]Section of Clinical Pathology, University of Bari, Bari 70124, Italy; E-Mails: azucano@ 123456libero.it (A.Z.); diseriofrancesca@ 123456tiscali.it (F.D.S.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: marcomatteo.ciccone@ 123456uniba.it ; Tel.: +39-080-547-8791; Fax: +39-080-547-8796.
                Article
                molecules-19-01651
                10.3390/molecules19021651
                6271201
                24481114
                59b332f0-f1cf-40bc-8992-60b21e736c6a
                © 2014 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 23 December 2013
                : 21 January 2014
                : 21 January 2014
                Categories
                Article

                carotid intima-media thickness,obstructive sleep apnea,high sensitive c-reactive protein,interleukin-6,tumor necrosis factor-alpha,pentraxin-3

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