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Case Reports
. 2010 Aug 21:5:66.
doi: 10.1186/1749-8090-5-66.

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 , Omer Sezer, Christian Vahlhaus, Horst Robenek, Andreas Hoffmeier, Tonny D T Tjan, Hans H Scheld, Jürgen R Sindermann
Affiliations
Case Reports

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 et al. J Cardiothorac Surg. .

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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Figures

Figure 1
Figure 1
Angiogram showing alternating dilatation and stenosis with irregularities of the aortic arch. Both subclavian and vertebral arteries are occluded. The truncus bracheocephalicus is aneurysmatically dilated.
Figure 2
Figure 2
Transverse (A) and sagittal (B) CT views of the aorta. The dissection (arrows) is circumferential and begins distally to the coronary ostiae. arrows: dissection membrane
Figure 3
Figure 3
Correlation between inflammatory infiltration and collagen degradation. Picro Siriusred staining (panel A: collagen deposition = red) showing areas with massive collagen degradation. Immunohistochemistry for CD68 (panel B) and 27E10 (panel C) demonstrated accumulation of infiltrating cells particularly at the intima-media border (arrows indicate areas with profound vascularization). MMP1 (panel D) and MMP9 (panel E) were strongly expressed at the intima-media border and in deeper areas of the media. Interestingly, MMP2 expression was only very low (not shown). In situ zymography (panel F: collagenolysis) showed massive collagenolytic activity at the intima-media border and in deeper areas of the media. (m: media; i: intima; original magnification: ×100)
Figure 4
Figure 4
Expression of collagenolytic MMPs as demonstrated by RT-PCR analyses. Our data show a strong upregulation of the mRNA expression of collagenase (MMP1) and both gelatinases (MMP2 and MMP9) (CSx) compared with controls (ctrl).
Figure 5
Figure 5
Expression of the GM-CSF system. A: Our data show a strong expression of GM-CSF at the intima-media border (arrows indicate areas with profound vascularization). B: RT-analyses revealed that not only GM-CSF but also its receptor subunits - the common receptor untit GM-CSF-receptor ß (GM-Rß) and both (-Subunits (GM-Ra1 and GM-Ra2) - are upregulated in CSx compared with controls (ctrl).
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References

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