Key result
The RTK-AKT pathway is significantly more activated in the medial layer of the ascending aorta in patients with bicuspid aortic valves compared to those with tricuspid aortic valves (P=0.0003), regardless of aortic dilation.
Observational (n=22)
No
p-value: p=0.0003
The RTK-AKT pathway is activated in the medial layer of the ascending aorta in patients with bicuspid aortic valve, which may contribute to tissue fragility and aortic dilatation.
Supports RTK-AKT targeting in BAV aortopathy; leaves open causality and clinical relevance pending prospective studies.
BACKGROUND: Dilatation of the ascending aorta affects those patients with bicuspid aortic valve (BAV), even after valvular surgery, possibly due to tissue fragility. The goal of the study was the molecular characterization of aorta with BAV compared to that with normal tricuspid aortic valve (TAV). METHODS AND RESULTS: The subjects were patients who underwent surgery for aortic valve stenosis in 2013 and 2014. Nine patients with BAV and 13 with TAV were examined. There was no difference in the clinical characteristics or grade of aortic valve stenosis, but the diameters of the ascending aorta were significantly higher in the BAV group. The ascending aortic specimens were subjected to transcriptome analyses, which revealed the changes in receptor tyrosine kinase (RTK) pathway-related genes between TAV and BAV samples. Immunohistochemical study revealed higher staining of phosphorylated AKT (pAKT) in the media of the ascending aorta in the BAV group, regardless of the size of ascending aorta, whereas total AKT did not show such a difference. Immunofluorescence staining revealed the AKT activation was mainly in the medial vascular smooth muscle cells. CONCLUSIONS: The results showed that the RTK-AKT pathway in the medial layer of the ascending aorta is activated in aortae with BAV. Activation of this pathway may be associated with fragility and dilatation of the ascending aorta with BAV.
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Hirata et al. (2018) conducted an observational in Aortic valve stenosis (n=22). Bicuspid aortic valve vs. Tricuspid aortic valve was evaluated on Phosphorylated AKT (pAKT) expression in the medial layer of the ascending aorta (p=0.0003). The RTK-AKT pathway is significantly more activated in the medial layer of the ascending aorta in patients with bicuspid aortic valves compared to those with tricuspid aortic valves (P=0.0003), regardless of aortic dilation.
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