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      Twisted Blood Vessels: Symptoms, Etiology and Biomechanical Mechanisms

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          Abstract

          Tortuous arteries and veins are commonly observed in humans and animals. While mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in distal organs. Clinical observations have linked tortuous arteries and veins with aging, atherosclerosis, hypertension, genetic defects and diabetes mellitus. However, the mechanisms of their formation and development are poorly understood. This review summarizes the current clinical and biomechanical studies on the initiation, development and treatment of tortuous blood vessels. We submit a new hypothesis that mechanical instability and remodeling could be mechanisms for the initiation and development of these tortuous vessels.

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          Most cited references118

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          Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo.

          Extracellular elastic fibres provide mechanical elasticity to tissues and contribute towards the processes of organ remodelling by affecting cell-cell signalling. The formation of elastic fibres requires the assembly and crosslinking of tropoelastin monomers, and organization of the resulting insoluble elastin matrix into functional fibres. The molecules and mechanisms involved in this process are unknown. Fibulin-5 (also known as EVEC/DANCE) is an extracellular matrix protein abundantly expressed in great vessels and cardiac valves during embryogenesis, and in many adult tissues including the aorta, lung, uterus and skin, all of which contain abundant elastic fibres. Here we show that fibulin-5 is a calcium-dependent, elastin-binding protein that localizes to the surface of elastic fibres in vivo. fibulin-5-/- mice develop marked elastinopathy owing to the disorganization of elastic fibres, with resulting loose skin, vascular abnormalities and emphysematous lung. This phenotype, which resembles the cutis laxa syndrome in humans, reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells. This function may be mediated by the RGD motif in fibulin-5, which binds to cell surface integrins, and the Ca2+-binding epidermal growth factor (EGF) repeats, which bind elastin.
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            Fibulin-5/DANCE is essential for elastogenesis in vivo.

            The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature.
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              Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group.

              To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-related variables were assessed at a core angiographic laboratory and at the clinical sites. Most patients had Canadian Cardiovascular Society class III or IV angina (72%) and two-vessel coronary disease (78%). Left ventricular function was generally well preserved (mean ejection fraction, 58 +/- 12%; range, 18-85%) and 1.9 +/- 1.0 stenoses per patient had attempted percutaneous coronary angioplasty. Procedural success (less than or equal to 50% final diameter stenosis in one or more stenoses and no major ischemic complications) was achieved in 290 patients (82.8%), and an additional nine patients (2.6%) had a reduction in diameter stenosis by 20% or more with a final diameter stenosis 51-60% and were without major complications. Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 30 patients (8.6%). In-hospital mortality was 1.1%. Stepwise regression analysis determined that a modified American College of Cardiology/American Heart Association Task Force (ACC/AHA) classification of the primary target stenosis (with type B prospectively divided into type B1 [one type B characteristic] and type B2 [greater than or equal to two type B characteristics]) and the presence of diabetes mellitus were the only variables independently predictive of procedural outcome (target stenosis modified ACC/AHA score; p less than 0.001 for both success and complications; diabetes mellitus: p = 0.003 for success and p = 0.016 for complications). Analysis of success and complications on a per stenosis dilated basis showed, for type A stenoses, a 92% success and a 2% complication rate; for type B1 stenoses, an 84% success and a 4% complication rate; for type B2 stenoses, a 76% success and a 10% complication rate; and for type C stenoses, a 61% success and a 21% complication rate. The subdivision into types B1 and B2 provided significantly more information in this clinically important intermediate risk group than did the standard ACC/AHA scheme. The stenosis characteristics of chronic total occlusion, high grade (80-99% diameter) stenosis, stenosis bend of more than 60 degrees, and excessive tortuosity were particularly predictive of adverse procedural outcome. This improved scheme may improve clinical decision making and provide a framework on which to base meaningful subgroup analysis in randomized trials assessing the efficacy of percutaneous coronary angioplasty.
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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2012
                May 2012
                14 March 2012
                : 49
                : 3
                : 185-197
                Affiliations
                Department of Mechanical Engineering and Biomedical Engineering Program, University of Texas at San Antonio, San Antonio, Tex., USA
                Author notes
                *Dr. Hai-Chao Han, Department of Mechanical Engineering, University of Texas at San Antonio, San Antonio, TX 78249 (USA), Tel. +1 210 458 4952, E-Mail hchan@utsa.edu
                Article
                335123 PMC3369246 J Vasc Res 2012;49:185–197
                10.1159/000335123
                PMC3369246
                22433458
                295222f9-099c-447e-a5d4-cbed7684a2fc
                © 2012 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 26 July 2011
                : 11 November 2011
                Page count
                Figures: 6, Tables: 1, Pages: 13
                Categories
                Review

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Mechanical buckling,Wall remodeling,Mechanical instability,Artery tortuosity,Vessel tortuosity

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