This article has Open Peer Review reports available.
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
- Gabriele Weissen-Plenz†1, 2,
- Ömer Sezer†1,
- Christian Vahlhaus3,
- Horst Robenek2,
- Andreas Hoffmeier1,
- Tonny DT Tjan1,
- Hans H Scheld1 and
- Jürgen R Sindermann1Email author
© Weissen-Plenz et al; licensee BioMed Central Ltd. 2010
Received: 10 February 2010
Accepted: 21 August 2010
Published: 21 August 2010
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.
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).
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.
Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease and vestibuloauditory symptoms [1, 2]. Major clinical features are interstitial keratitis and vestibuloauditory dysfunction. The variety of systemic manifestations includes fever, splenomegaly, lymphadenopathy, and musculoskeletal complaints. Systemic vasculitis is found in about 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. Aortic aneurysms due to aortitis often refrain from being recognized in Cogan's syndrome, and are potentially fatal, with two of eight reported cases dying from aneurysm/arterial rupture [3, 4]. To the best of our knowledge, Cogan's syndrome complicated by aortic dissection as mirrored by the present paper has not been described in detail yet.
Taken together, our data on vascular matrix integrity and expression of the major matrix molecules indicate that although both collagen and elastin production was stimulated in SMC, the even greater increase in MMP activity in both inflammatory cells and SMC resulted in exceeding elastolysis and collagenolysis and thus a dramatic loss of structural integrity.
Interestingly, in areas of exceeding matrix deterioration the level of GM-CSF, a proinflammatory mediator and important regulator of the vascular collagen and elastin metabolism [5, 6], was massively increased.
In summary, 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. GM-CSF is a regulator of vascular collagen and elastin metabolism. In mice with genetically modulated GM-CSF-expression adverse remodeling of the vascular extracellular matrix was found [5, 6]. Therefore, overstimulation of the GM-CSF-system as found in our patient may present the underlying trigger of adverse extracellular matrix remodeling, loss of functional texture (in the areas of persistent inflammation) and thus contribute to the destabilization of the aortic wall finally leading to aortic dissection.
Cogan's syndrome complicated by aortic dissection has not been described in detail yet. The herein presented case of a 46-year old female suggests that overstimulation of the GM-CSF-system may function as an underlying trigger of adverse extracellular matrix remodeling and loss of functional texture. These features may contribute to the destabilization of the aortic wall which may provide a mechanism leading to aortic dissection in a number of vascular diseases.
The study was approved by the local Review board of the University of Muenster. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Gluth MB, Baratz KH, Matteson EL, Driscoll CL: Cogan syndrome: a retrospective review of 60 patients throughout a half century. Mayo Clin Proc. 2006, 81: 483-488. 10.4065/81.4.483.View ArticlePubMedGoogle Scholar
- Gaubitz M, Lübben B, Seidel M, Schotte H, Gramley F, Domschke W: Cogan's syndrome: organ-specific autoimmune disease or systemic vasculitis? A report of two cases and review of the literature. Clin Exp Rheumatol. 2001, 19 (4): 463-469.PubMedGoogle Scholar
- Bisdas TE, Teebken OE, Wilhelmi M, Lotz J, Bredt M, Haverich A, Pichlmaier MA: Surgical treatment of a thoracoabdominal aneurysm in Cogan's syndrome. Ann Thorac Surg. 2009, 88: 1668-1670. 10.1016/j.athoracsur.2009.04.081.View ArticlePubMedGoogle Scholar
- Low AH, Su JW, Sin KY, Fong KY, Thumboo J: Cogan's syndrome with recurrent carotid and aortic aneurysms: a potentially fatal disorder mimicking Marfan syndrome. Scand J Rheumatol. 2007, 36: 71-73. 10.1080/03009740600907923.View ArticlePubMedGoogle Scholar
- Plenz G, Eschert H, Beissert S, Arps V, Sindermann JR, Robenek H, Völker W: Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice. FASEB J. 2003, 17: 1451-1457. 10.1096/fj.02-1035com.View ArticlePubMedGoogle Scholar
- Weissen-Plenz G, Eschert H, Volker W, Sindermann JR, Beissert S, Robenek H, Scheld HH, Breithardt G: Granulocyte macrophage colony-stimulating factor deficiency affects vascular elastin production and integrity of elastic lamellae. J Vasc Res. 2008, 45: 103-110. 10.1159/000109819.View ArticlePubMedGoogle Scholar
This article is published under license to 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.