The role of transforming growth factor beta in bicuspid aortic valve aortopathy

Figures

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  Fig. 1. Transverse histological section of a non-dilated tricuspid ascending aorta. Sections (5 μm) are stained with Movat pentachrome staining (A, D, E, G), alpha smooth muscle actin (B), and hematoxylin eosin (C, F). The intima, media, and adventitia are depicted in the overview figure. Details of the vascular components are shown in the inserts. The vascular SMCs are shown in the alpha smooth muscle actin–stained section (B), vasa vasorum in the medial layer is shown in the hematoxylin and eosin–stained section (C), and an atherosclerotic plaque in the intimal layer is highlighted in the Movat-stained section in D. E A detailed view of vasa vasorum in the adventitial layer. A nerve cell (F) and clustered adipocytes (G) are further shown in a hematoxylin and eosin- and Movat-stained sections, respectively. HE, hematoxylin and eosin; αSMA, alpha smooth muscle actin; SMC, smooth muscle cell. Scale bars shown in figure

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  Fig. 2. Transverse histological Section (5 μm) of a tricuspid non-dilated ascending aortic wall stained with hematoxylin and eosin (A), alpha smooth muscle actin (B), and resorcin fuchsin (C). The intimal layer is depicted with the red dashed line. The intima is filled with fine elastic lamellae and is devoid of alpha smooth muscle actin expression. HE, hematoxylin and eosin; αSMA, alpha smooth muscle actin; RF, resorcin fuchsin. Scale bars shown in figure

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  Fig. 3. Schematic overview of the transforming growth factor beta (TGF-β) signaling pathway linked to matrix metalloproteinase (MMP) production. Activated TGF-β from the latent complex binds to its cell surface receptor II (TGFβRII), inducing the activation of TGF-β type I receptor (TGFβRI). The then activated TGFβRI phosphorylates SMAD2,3. SMAD7 on the other hand inhibits the TGF-β signaling at the receptor level. Phosphorylated SMADs interact with co-SMAD4 which induces the production of MMP2 and tissue inhibitors of matrix metalloproteinases (TIMPs). Created with Biorender.com

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  Fig. 4. Transverse histological section (5 μm) of a dilated bicuspid ascending aorta (Movat pentachrome staining — A, B, D and resorcin fuchsin staining — C). The intima, media, and adventitia are depicted in the overview figure. Details of the vascular components are shown in the inserts. The intimal layer is shown in Fig. 4B; the white dashed line depicts the border between the intima and the media. The fine elastic lamellae in the media are shown in Fig. 4C, with hardly any fragmentation. In Fig. 4D, the Movat-stained medial layer shows elastic lamellae in black, vascular smooth muscle cells in red, and an abundance of mucoid extracellular matrix in blue between the elastic lamellae. RF, resorcin fuchsin. Scale bars shown in figure