Endothelial function and plasma matrix metalloproteinase‐2 levels and their association with the size and elastic properties of the ascending aorta in first‐degree relatives of bicuspid aortic valve patients

AimsTo compare the stiffness index in patients with bicuspid aortic valve (BAV) with first-degree relatives at each segment of the thoracic ascending aorta and to compare segmental analysis of aortic stiffness in association with BAV morphotype and function.Methods219 patients with BAV and 148 first-degree relatives (without BAV) were consecutively included at a reference centre for BAV. Ultrasound assessment of aortic and carotid stiffness was based on the variation of the segmental arterial diameters during the cardiac cycle and on blood pressure.ResultsWithout adjustment, the ascending aorta of patients with BAV seemed stiffer at each segment compared with controls (stiffness index at the sinus of Valsalva: 17.0±10.9 vs 8.9±6.1, p<0.001; tubular aorta: 20.4±31.3 vs 12.7±4.8, p=0.04). However, after adjustment on aortic diameter and age, only the sinus of Valsalva remained stiffer (p<0.001), whereas the tubular aorta no longer differed (p=0.610). In patients with BAV, aortic diameters were not influenced by the valve morphotype, except for the arch, which was more dilated in the case of 1- Non coronary sinus-Right subtype of BAV : 36.1 vs 27.6 mm, p<0.001. Aortic regurgitation was associated with an increase in aortic diameters at the sinus of Valsalva (p<0.001) and the tubular aortic levels (p=0.04).ConclusionStiffness increase at the sinus of Valsalva level is independent of aortic dilatation in patients with BAV, contrary to the classic relationship between stiffness and dilatation found on the other segments. The relationship between stiffness and clinical impact needs to be assessed at each aortic segment.

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Aortic assessment of bicuspid aortic valve patients and their first-degree relatives

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492317696375 ◽

2017 ◽

Vol 25 (3) ◽

pp. 192-198

Author(s):

Pablo Straneo ◽

Gabriel Parma ◽

Natalia Lluberas ◽

Alvaro Marichal ◽

Gerardo Soca ◽

...

Keyword(s):

Aortic Valve ◽

Endothelial Function ◽

Bicuspid Aortic Valve ◽

Aortic Root ◽

Inverse Correlation ◽

Hereditary Disease ◽

Root Diameter ◽

Aortic Dilatation ◽

First Degree Relatives ◽

Increased Risk

Background Bicuspid aortic valve patients have an increased risk of aortic dilatation. A deficit of nitric oxide synthase has been proposed as the causative factor. No correlation between flow-mediated dilation and aortic diameter has been performed in patients with bicuspid aortic valves and normal aortic diameters. Being a hereditary disease, we compared echocardiographic features and endothelial function in these patients and their first-degree relatives. Methods Comprehensive physical examinations, routine laboratory tests, transthoracic echocardiography, and measurements of endothelium-dependent and non-dependent flow-mediated vasodilatation were performed in 18 bicuspid aortic valve patients (14 type 1 and 4 type 2) and 19 of their first-degree relatives. Results The first-degree relatives were younger (36.7 ± 18.8 vs. 50.5 ± 13.9 years, p = 0.019) with higher ejection fractions (64.6% ± 1.7% vs. 58.4% ± 9.5%, p = 0.015). Aortic diameters indexed to body surface area were similar in both groups, the except the tubular aorta which was larger in bicuspid aortic valve patients (19.3 ± 2.7 vs. 17.4 ± 2.2 mm·m−2, p = 0.033). Flow-dependent vasodilation was similar in both groups. A significant inverse correlation was found between non-flow-dependent vasodilation and aortic root diameter in patients with bicuspid aortic valve ( R = −0.57, p = 0.05). Conclusions Bicuspid aortic valve patients without aortopathy have larger ascending aortic diameters than their first-degree relatives. Endothelial function is similar in both groups, and there is no correlation with ascending aorta diameter. Nonetheless, an inverse correlation exists between non-endothelial-dependent dilation and aortic root diameter in bicuspid aortic valve patients.

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Usefulness of Bicuspid Aortic Valve Phenotype to Predict Elastic Properties of the Ascending Aorta

The American Journal of Cardiology ◽

10.1016/j.amjcard.2006.09.118 ◽

2007 ◽

Vol 99 (5) ◽

pp. 686-690 ◽

Cited By ~ 106

Author(s):

Benjamin M. Schaefer ◽

Mark B. Lewin ◽

Karen K. Stout ◽

Peter H. Byers ◽

Catherine M. Otto

Keyword(s):

Aortic Valve ◽

Elastic Properties ◽

Bicuspid Aortic Valve ◽

Ascending Aorta

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Matrix Metalloproteinase-2 Isoforms Differ within the Aortic Wall of Ascending Aortic Aneurysms Associated with Bicuspid Aortic Valve

Cardiology Research and Practice ◽

10.1155/2020/1306425 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ramona Schmitt ◽

Anke Tscheuschler ◽

Philipp Laschinski ◽

Philipp Discher ◽

Jana Fuchs ◽

...

Keyword(s):

Aortic Valve ◽

Matrix Metalloproteinase ◽

Bicuspid Aortic Valve ◽

Aortic Wall ◽

Aortic Aneurysms ◽

Matrix Metalloproteinase 2 ◽

Enzyme Linked Immunosorbent Assay ◽

Tissue Levels ◽

Protein Levels ◽

Underlying Pathogenesis

The pathogenesis of ascending thoracic aortic aneurysm (aTAA) is thought to differ between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV), and one of the causes is different hemodynamics. Influenced by hemodynamics, the tissue levels of proteins associated with aTAA might differ between aTAAs with BAV and TAV and between different localities within the aortic wall. We therefore analyzed aTAA tissue levels of MMP-2 (matrix metalloproteinase-2) isoforms (Pro-MMP-2, active MMP-2, and total MMP-2) and tissue levels of MMP-14, TIMP-2 (tissue inhibitor of metalloproteinase-2), MMP-9, and TIMP-1 in 19 patients with BAV and 23 patients with TAV via gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. TAV and BAV groups’ protein levels did not differ significantly. Whereas the TAV group exhibited no significant differences in protein levels between the aneurysm’s anterior and posterior parts, the BAV group revealed significantly higher levels of Pro-MMP-2, total MMP-2, and TIMP-2 in the aneurysm’s posterior parts (mean Pro-MMP-2 200.52 arbitrary units (AU) versus 161.12 AU, p=0.007; mean total MMP-2 235.22 AU versus 193.68 AU, p=0.002; mean TIMP-2 26.90 ng/ml versus 25.36 ng/ml, p=0.009), whereas the other proteins did not differ significantly within the aortic wall. Thus, MMPs are distributed more heterogeneously within the aortic wall of aTAAs associated with BAV than in those associated with TAV, which is a new aspect for understanding the underlying pathogenesis. This heterogeneous protein level distribution might be attributable to differences in the underlying pathogenesis, especially hemodynamics. This result is important for further studies as it will be essential to specify the location of samples to ensure data comparability regarding the main goals of understanding the pathogenesis of aTAA, optimizing treatments, and establishing a screening method for its potentially deadly complications.

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