Abstract 15474: Differential Proteoglycan Expression Contributes to the Pathogenesis of Heritable Aortic Aneurysm Formation
Excessive proteoglycan (PG) accumulation is a distinct feature of heritable thoracic aortic aneurysms (TAA), damaging the elastic lamellar units. PGs have both mechanical and signaling roles. Versican, perlecan and decorin can be upregulated by TGFβ signaling in various disease states. Increased TGFβ signaling is implicated in the pathogenesis of Bicuspid Aortic Valve (BAV) and Marfan Syndrome (MFS) associated thoracic aortic aneurysms (TAA). Perlecan organizes the endothelial BM and elastic lamellae and inhibits VSMC proliferation. Versican forms a loose matrix and its degradation products can alter VSMC proliferation. Biglycan and decorin have overlapping roles in fibrillogenesis, collagen assembly and TGFβ sequestration. We hypothesized that in both BAV-TAA and MFS-TAA PG expression will be altered and may exacerbate TAA pathogenesis. Computational immunohistochemistry was used to quantify PG expression in aortic tissue from human BAV-TAA (n=8), human MFS-TAA (n=8) and controls (n=5). Perlecan expression was increased (p<0.01) in BAV-TAA but decreased (p<0.01) in MFS-TAA medial tissue compared to controls. The expression of versican was increased (p<0.03) in both BAV- and MFS-TAA medial tissue compared to controls. However, biglycan expression was decreased (p<0.01) in both BAV- and MFS-TAA medial tissue compared to controls. Interestingly, the expression of decorin was increased (p<0.03) in the media, but decreased (p<0.05) in the adventitia of both BAV- and MFS-TAA tissue compared to controls, while the levels of expression of the other three PG did not change in the adventitia. Moreover, no significant difference was found between MFS- and BAV-TAA in any of the PG expression. TAA is thought to be due to excessive TGFβ signaling, consistent with a rise in versican and decorin. However, perlecan fell in MFS but rose in BAV. The fall in MFS may be due to the functional reduction of binding partner fibrillin. The fall in biglycan may reflect global destruction of medial elastic lamellae, with a compensatory rise in decorin as part of a fibrotic response. Together, these alterations contribute to the pathogenesis of TAA and reinforce the central role of TGFβ signaling and support the use of angiotensin II receptor blockers.
Author Disclosures: M. Emami: None. J.W. Trompf: None. E. Robertson: None. S.S. Portelli: None. Y. Lu: None. S. Maleki: None. C. McLachlan: None. M. Kekic: None. S. Bao: None. B.D. Hambly: None. R. Jeremy: None.
- © 2016 by American Heart Association, Inc.