Type A dissection and chronic dilatation: tenascin-C as a key factor in destabilization of the aortic wall

Abstract

Objectives: Tenascin-C plays an important role in myocardial and vascular remodelling. We hypothesized that tenascin-C is a key factor in the development of degenerative disease of the ascending aorta, leading to chronic dilatation and acute aortic dissection.

Methods: Ascending aortic wall specimens were obtained during surgery for chronic dilatation (n=52) and acute Type A dissection (n=30). Patients (n=12) undergoing aortic valve replacement served as controls. Tenascin-C expression was evaluated by immunostaining and semi-quantitatively assessed using the ImageJ software. TN-C levels in peripheral blood were determined by enzyme-linked immunosorbent assay.

Results: Histological examination showed a clear difference between chronic dilatation and acute dissection. In chronic dilatation, tenascin-C staining was homogenously distributed throughout the media parallel to vascular smooth muscle cells. In acute dissection, a strong staining with a heterogenous and spotty distribution was detected. Control aortas showed no tenascin-C staining. Tenascin-C expression was significantly higher in Type-A dissection compared with chronic dilatation. This was accompanied by a significant elevation of tenascin-C levels in peripheral blood in acute dissection. There was no statistical correlation between the tenascin-C level in peripheral blood and the aortic diameter either in dissection or in dilatation.

Conclusions: Tenascin-C is a marker of progressive destabilization of the aortic wall independent of size in chronic dilatation and acute dissection. Therefore, it might be a valuable tool in guiding intervention strategies in patients with disease of the ascending aorta.

Keywords: Aorta/aortic pathology; Aortic aneurysm; Aortic dissection.

Figure 1:

Representative images in hematoxylin-eosin (HE), elastica staining and tenascin-C (TN-C) immunohistochemistry (magnification ×100). (A) In acute dissection, HE and elastica staining show the typical picture of cystic media necrosis (CMN) with loss of media myocytes, accumulation of extracellular matric (ECM) with the formation of cystic structures and disruption of elastic fibres. TN-C staining is strong with a very heterogenous and spotty distribution. (B1–B3) show the three different staining patterns found in chronic dilatation: In (B1), signs of CMN in HE and elastica staining are present with homogenous distribution of TN-C staining throughout the media oriented parallel to the media myocytes. In (B2), severe signs of CMN in HE and elastica staining are accompanied by a strong and spotty TN-C staining similar to the picture in acute dissection. (B3) shows a normal aortic wall in HE and elastica staining without TN-C positive staining of the media. All control patients (C) have a normal aortic wall in HE and elastica staining with a TN-C negative media.

Figure 2:

(A) Tenascin-C (TN-C) expression by semi-quantitative assessment of TN-C immunohistochemistry in five random areas per section using the ImageJ software. Data are given as percent area of the total field. **P = 0.002 dissection vs dilatation; P = 0.25 dilatation vs control; P = 0.03 dissection vs control; F = 0.04 (B) TN-C levels in peripheral blood immediately before surgery assessed by ELISA. **P < 0.001 dissection vs dilatation, P = 0.44 dilatation vs control, P = 0.002 dissection vs control. Data are depicted as boxplots, boxes represent the inter-quartile range and whiskers define the minimum to maximum, line at median.

Figure 3:

There is no statistical correlation between aortic diameter and plasma tenascin-C (TN-C) levels immediately before surgery neither in chronic dilatation (A) nor in acute dissection (B) according to Pearson r testing (alpha = 0.05).