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Elastin degradation is dependent upon transforming growth factor-beta ligand in tricuspid (TAV), but not bicuspid (BAV) or unicuspid (UAV) aortic aneurysms. (A) Photomicrographs of ascending aortic cross-sections labeled with Movat’s pentachrome, depicting elastin (black filaments) breaks and degradation in BAV aortas. Blue stain represents mucoid extracellular matrix deposition. (B) Graph depicting elastin breaks in non-dilated (ND) aortas from individuals with a TAV, BAV or UAV. (C) Graph depicting the relationship between elastin breaks and maximal ascending aortic diameter in TAV (blue) and BAV/UAV (pink) aortas. (D) Graphs depicting the relationships between TGFß1 ligand concentration (whole aorta: left, medial layer: right) and elastin breaks in TAV (blue) and BAV/UAV (pink) aortas. (E) Graphs depicting the TGFß1 ligand concentration in ascending aortas with mild elastin loss (EL) and severe EL for TAV (left) and BAV/UAV (right) aortas. *P < 0.05. Scalebar = 50 µm. Fluores. = fluorescence.
Source publication
We sought to determine whether there are differences in transforming growth factor-beta (TGFß) signaling in aneurysms associated with bicuspid (BAV) and unicuspid (UAV) aortic valves versus normal aortic valves. Ascending aortic aneurysms are frequently associated with BAV and UAV. The mechanisms are not yet clearly defined, but similarities to tra...
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Citations
... Murine genetics studies have shown that a loss of TGF-β signaling components generally leads to abnormal differentiation and maturation of the primitive vascular network, including a failure of SMC recruitment and/or differentiation [58]. Medial accumulation of mucoid extracellular matrix components is significantly higher in non-dilated and dilated BAV patients as compared to the TAV (Fig. 4D) [37,59]. ...
A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-β) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients.
... It is known that rs17684886 in ZNRF1 is associated with diabetic retinopathy [81], and its expression is induced in peripheral nerves after injury [82], so its overexpression causes neurite-like elongation. It has been found that expression of the SMAD2 protein is progressively increased in reactive lesions and oral submucous fibrosis (OSMF) [83], and SMAD3 contributes to ascending aortic dilatation independently of transforming growth factor-beta in bicuspid and unicuspid aortic valve disease [84], which is consistent with our data. ...
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