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      Aortic dissection associated with cogans's syndrome: deleterious loss of vascular structural integrity is associated with GM-CSF overstimulation in macrophages and smooth muscle cells

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          Abstract

          Background

          Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease and vestibuloauditory symptoms. Systemic vasculitis is found in about 10% of cases.

          Case presentation

          A 46-year-old female with Cogans's syndrome and a history of arterial hypertension presented with severe chest pain caused by an aneurysm of the ascending aorta with a dissection membrane located a few centimeters distal from the aortic root. After surgery, histopathological analysis revealed that vascular matrix integrity and expression of the major matrix molecules was characterized by elastolysis and collagenolysis and thus a dramatic loss of structural integrity. Remarkably, exceeding matrix deterioration was associated with massively increased levels of granulocyte macrophage colony stimulating factor (GM-CSF).

          Conclusion

          Our data suggest that the persistently increased secretion of the inflammatory mediator GM-CSF by resident inflammatory cells but also by SMC may be the trigger of aortic wall structural deterioration.

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          Most cited references6

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          Cogan syndrome: a retrospective review of 60 patients throughout a half century.

          To evaluate the disease manifestations and clinical course of patients affected by Cogan syndrome (a syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms) at a single institution during roughly a half century. Medical records of all patients diagnosed as having Cogan syndrome at the Mayo Clinic in Rochester, Minn, and who were followed up from 1940 to 2002 were comprehensively reviewed. Otolaryngologic, ophthalmologic, and systemic manifestations of disease were analyzed. Analysis included patient demographics, presenting manifestations, delayed manifestations, laboratory testing, physical examination features, therapeutic interventions, disease course, and hearing and vision outcomes. Sixty patients were identified as having Cogan syndrome, with follow-up from 1940 to 2002. Most patients presented initially with vestibuloauditory symptoms, most commonly sudden hearing loss (50%). The most common inflammatory ophthalmologic condition noted was bilateral interstitial keratitis. Headache (40%), fever (27%), and arthralgia (35%) were the most frequently encountered systemic manifestations. Evidence of aortitis was found in 12% of patients. Complete hearing loss was eventually noted in 52% of affected patients, whereas permanent loss of any degree of vision was uncommon. Cochlear implantation outcomes were uniformly good. Death directly or indirectly attributed to the effects of Cogan syndrome was noted in 4 patients. The major disease-related morbidities were due to vestibuloauditory disease and only infrequently due to systemic manifestations such as vasculitis, with or without aortitis. Cochlear implantation has been of major benefit in modern hearing rehabilitation for this patient population. We advise caution before institution of protracted courses of high-dose corticosteroids and/or chemotherapy for patients without pronounced systemic disease or severe eye disease unmanageable by topical or periocular corticosteroids alone.
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            Cogan's syndrome: organ-specific autoimmune disease or systemic vasculitis? A report of two cases and review of the literature.

            Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory eye disease and vestibuloauditory symptoms. Typically, young adults suffer from interstitial keratitis and sudden onset of tinnitus and hearing loss. Few cases (around 150) have been published and thus it is difficult to determine the percentage of patients with underlying systemic disorders such as systemic vasculitis. The variety of systemic manifestations is large and includes fever, splenomegaly, lymphadenopath, and musculoskeletal complaints. Systemic vasculitis can be seen in around 10% of cases and may involve the large vessels, appearing as Takayasu-like vasculitis with affection of the aortic valve but also the coronary arteries and the small kidney vasculature. Evaluating the exact extension of the systemic features determines the choice of treatment. While corticosteroids have proved to be of short-term benefit, long-term treatment with immunosuppressive drugs is controversial. Auditory function in deaf patients has often been restored successfully with cochlear implants. To illustrate the nature of the syndrome, we present two patients with a wide clinical spectrum of symptoms from local disease restricted to the eyes and ears to a widespread vasculitis affecting arteries of the brain, kidney and the upper and lower extremities. We then review the typical aspects as well as the etiology of the disease.
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              Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice.

              GM-CSF takes part in the cytokine network regulating the metabolism of extracellular matrix (ECM) during atherogenesis. Since data also point to an effect of GM-CSF on the vascular ECM in general, the vascular collagenous matrix was studied in wild-type and GM-CSF-deficient mice. Histological examination revealed a disorganized vascular ECM in GM-CSF-deficient mice involving the collagenous matrix and elastic fiber system. As shown by electron microscopy, collagen bundles were disrupted and reduced. The diameter of fibrils varied widely. mRNA expression of collagens and related molecules was studied. Fibrillar collagens were markedly reduced, alpha1(I)procollagen to 16.5% of control levels alpha1(III)procollagen was abolished whereas the expression level of network-forming alpha1(VIII)procollagen was not altered. As shown by in situ hybridization, the number of collagen-expressing cells was reduced. Matrix metalloproteinases and their inhibitor 1 were not affected by GM-CSF deficiency. Our studies demonstrate that GM-CSF plays a major role in the cytokine network regulating the metabolism of vascular collagens. GM-CSF deficiency leads to an altered composition of the vascular collagenous matrix, i.e., reduced amount of fibrillar collagen, altered ratio of fibrillar and network-forming collagen, and failures in the fibrillogenesis. We suggest that GM-CSF is a basic requirement for the maintenance of vessel wall integrity and resilience.
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                Author and article information

                Journal
                J Cardiothorac Surg
                Journal of Cardiothoracic Surgery
                BioMed Central
                1749-8090
                2010
                21 August 2010
                : 5
                : 66
                Affiliations
                [1 ]Department of Thoracic and Cardiovascular Surgery, University Hospital of Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany
                [2 ]Leibniz Institute for Arteriosclerosis Research, Domagkstrasse 3, 48149 Muenster, Germany
                [3 ]Department of Cardiology and Angiology, University Hospital of Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany
                Article
                1749-8090-5-66
                10.1186/1749-8090-5-66
                2933604
                20727201
                fbb26696-d231-4753-8870-360ca1f9440f
                Copyright ©2010 Weissen-Plenz et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 February 2010
                : 21 August 2010
                Categories
                Case Report

                Surgery
                Surgery

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