Tricuspid Aortic Valve Groups Research Articles

EComment. Evaluating aortic media changes in ascending aorta aneurysm with bicuspid aortic valve disease

We read with great interest the paper by Girdauskas and colleagues who found that patients with bicuspid aortic valve (BAV) insufficiency and a proximal aorta of ≥50 mm had a significantly higher rate of moderate/severe proximal aortic media elastic fibre loss as compared to their counterparts with BAV stenosis [1]. We would like to add some thoughts about other fields of investigation between patients with BAV stenosis versus BAV insufficiency and ascending aorta aneurysms. The role of transforming growth factor β (TGFβ) pathway (expression of TGFβR1 and TGFβR2) could be evaluated in BAV stenosis versus BAV insufficiency groups with ascending aorta aneurysms. Forte et al. showed an increased TGFβ and TGFβR2 expression in mildly dilated ascending aortas in BAV stenosis and tricuspid aortic valve stenosis groups and also a decreased TGFβR1 expression only in BAV [2]. The existence of difference or not of the expression of extra domain-A splicing variant of fibronectin in BAV stenosis versus BAV insufficiency groups is an interesting issue as it was shown that its expression was activated in the media of mildly dilated BAV and tricuspid aortic valve (TAV) [2]. Another topic is the evaluation of smooth muscle cell (SMCs) phenotype and orientation in ascending aorta samples (both aortic curvatures) in BAV stenosis versus BAV insufficiency groups as different flow derangements and shear stress anomalies might be observed in these patients. Is there a different pattern of ascending aorta medial remodelling in these groups? Smooth muscle cells switched their phenotype in mildly dilated BAV and tricuspid aortic valve (TAV) [2]. Smoothelin and myocardin mRNAs decreased in all samples from BAV and TAV, with the exception of BAV convexity. There was also a change in orientation of smoothelin-positive SMCs and an increase of α-smooth muscle actin mRNA [2]. The expression of genes that are involved in extracellular matrix remodelling is another field which we could search for differences of expression of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metelloproteinases-2, MMP-9 and other MMPs in BAV stenotic versus BAV insufficiency groups. The MMP-2 mRNA was increased in the convexity of mildly dilated ascending aortas of BAV and TAV groups [2]. Differences in the biosynthesis of collagen and cross-linking in ascending aorta aneurysm of patients with BAV stenosis versus BAV insufficiency is another field of investigation. Are there any differences in collagen turnover in BAV stenosis versus BAV insufficiency groups? It was found that similar collagen turnover rates were observed in dilated and non-dilated aortas of BAV patients [3]. Is the nature of proximal aortic aneurysm (collagen biosynthesis and cross-linking) similar in BAV stenotic and BAV insufficiency groups? Is the collagen network similar in both groups? What about the ratio of hydroxylysyl pyridiholine to lysyl pyridinoline, two distinct forms of collagen cross-linking? Is there any defect in post-translational collagen modification? In dilated aortas from patients with BAV a deficiency was found at the level of lysyl hydroxylase (PLOD1) which showed reduced PLOD1 expression [3]. Could microRNA (miR)-29 expression be involved in the ascending thoracic aorta with aneurysm progression in BAV patients? It was demonstrated that decreased levels of miR-29b in the aortic wall could attenuate aortic aneurysm progression in two different mouse models of abdominal aortic aneurysms [4]. BAV-related ascending aorta dilation represent a potential field of investigation for future research. Conflict of interest: none declared.

Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease

Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilation that progresses to rupture if left undetected and untreated. If detected, patients with TAA are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging because no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAVs), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). In addition, altered microRNA (miR) expression levels have also been reported in TAAs compared with normal aortic tissue. The objective of our study was to identify circulating factors within plasma that could serve as potential biomarkers for distinguishing etiologic subtypes of aneurysm disease. Ascending TAA tissue and plasma specimens were obtained from patients with BAV (n=21) and TAV (n=21) at the time of surgical resection. The protein abundance of key MMPs (1, 2, 3, 8, and 9), TIMPs (1, 2, 3, and 4), and miRs (1, 21, 29a, 133a, 143, and 145) was examined using a multianalyte protein profiling system or by quantitative polymerase chain reaction, respectively. Results were compared with normal aortic tissue and plasma obtained from patients without aortic disease (n=10). Significant (P<.05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis revealed significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMP-1, TIMP-3, and TIMP-4 (P<.05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, MMP-2, and MMP-7, and for decreased MMP-8 and MMP-9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and MMP-9. Taken together, these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized strategies to distinguish between etiologic subtypes of TAAs in patients with aneurysm disease.