Enlarged Size and Impaired Elastic Properties of the Ascending Aorta are Associated with Endothelial Dysfunction and Elevated Plasma Matrix Metalloproteinase-2 Level in Patients with Bicuspid Aortic Valve

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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Endothelial Function, Carotid–Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2009.08.080 ◽

2010 ◽

Vol 55 (7) ◽

pp. 660-668 ◽

Cited By ~ 81

Author(s):

Nikolaos Tzemos ◽

Erik Lyseggen ◽

Candice Silversides ◽

Michal Jamorski ◽

Jeffrey H. Tong ◽

...

Keyword(s):

Aortic Valve ◽

Matrix Metalloproteinase ◽

Endothelial Function ◽

Bicuspid Aortic Valve ◽

Matrix Metalloproteinase 2

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Collagen analysis in aneurysmal ascending aorta obtained from patients with bicuspid aortic valve disease compared with tricuspid aortic valve aneurysm

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0034-1367284 ◽

2014 ◽

Vol 62 (S 01) ◽

Author(s):

A. Navarrete Santos ◽

P. Lochmann ◽

J.Y. Yan ◽

A. Simm ◽

R.-E. Silber ◽

...

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Aortic Valve Disease ◽

Ascending Aorta ◽

Valve Disease ◽

Tricuspid Aortic Valve ◽

Collagen Analysis

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Faculty Opinions recommendation of Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718288683.793540036 ◽

2017 ◽

Author(s):

Cheng-Hock Toh

Keyword(s):

Systemic Lupus Erythematosus ◽

Endothelial Dysfunction ◽

Matrix Metalloproteinase ◽

Lupus Erythematosus ◽

Neutrophil Extracellular Traps ◽

Matrix Metalloproteinase 2 ◽

Systemic Lupus ◽

Extracellular Traps

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Bicuspid aortic valve morphology and aortic valvular outflow jets: an experimental analysis using an MRI-compatible pulsatile flow circulation system

Scientific Reports ◽

10.1038/s41598-021-81845-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kaoru Hattori ◽

Natsuki Nakama ◽

Jumpei Takada ◽

Gohki Nishimura ◽

Ryo Moriwaki ◽

...

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Pulsatile Flow ◽

Aortic Wall ◽

Ascending Aorta ◽

Circulation System ◽

Resonance Imaging ◽

Left Posterior ◽

Flow Circulation ◽

The Right

AbstractThe characteristics of aortic valvular outflow jet affect aortopathy in the bicuspid aortic valve (BAV). This study aimed to elucidate the effects of BAV morphology on the aortic valvular outflow jets. Morphotype-specific valve-devising apparatuses were developed to create aortic valve models. A magnetic resonance imaging-compatible pulsatile flow circulation system was developed to quantify the outflow jet. The eccentricity and circulation values of the peak systolic jet were compared among tricuspid aortic valve (TAV), three asymmetric BAVs, and two symmetric BAVs. The results showed mean aortic flow and leakage did not differ among the five BAVs (six samples, each). Asymmetric BAVs demonstrated the eccentric outflow jets directed to the aortic wall facing the smaller leaflets. In the asymmetric BAV with the smaller leaflet facing the right-anterior, left-posterior, and left-anterior quadrants of the aorta, the outflow jets exclusively impinged on the outer curvature of the ascending aorta, proximal arch, and the supra-valvular aortic wall, respectively. Symmetric BAVs demonstrated mildly eccentric outflow jets that did not impinge on the aortic wall. The circulation values at peak systole increased in asymmetric BAVs. The bicuspid symmetry and the position of smaller leaflet were determinant factors of the characteristics of aortic valvular outflow jet.

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