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

2010 ◽  
Vol 55 (7) ◽  
pp. 660-668 ◽  
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

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

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.

Matrix Metalloproteinase-2 and -9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve

2012 ◽  
Vol 30 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Okay Abaci ◽  
Cuneyt Kocas ◽  
Kadriye Orta Kilickesmez ◽  
Sinan Uner ◽  
Serdar Kucukoglu
Keyword(s):  
Aortic Valve ◽  
Matrix Metalloproteinase ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Matrix Metalloproteinase 2

Abstract 15097: Altered TGFβ Signalling Effector Molecules Contribute to Bicuspid Aortic Valve-associated Thoracic Aortopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Candice L Dilworth ◽  
Francesca Sadnick ◽  
Sari Padang ◽  
Yaxin Lu ◽  
Elizabeth N Robertson ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Aneurysms ◽  
Extra Cellular Matrix ◽  
Matrix Metalloproteinase 2 ◽  
Compensatory Mechanism ◽  
Aortic Dilatation ◽  
Matrix Degradation ◽  
Tgfβ Signalling ◽  
Cellular Matrix

Upregulated TGFβ signalling plays a key role in mediating congenital thoracic aortic aneurysms (TAA), and has been implicated in bicuspid aortic valve-associated TAA (BAV-TAA). TGFβ is normally stored within the extra-cellular matrix via sequestration proteins bound to the microfibrillar protein, fibrillin. TGFβ is released in response to changes in these sequestration proteins, allowing TGFβ to exert its signalling effects. We hypothesised that in BAV-TAA the upregulation of TGFβ signalling will pathologically alter effector molecule expression, causing matrix degradation and altered TGFβ sequestration. Immunohistochemistry was used to quantify protein expression in aortic tissue from 8 human BAV-TAA and 6 normal controls. In BAV-TAA, TGFβ expression was elevated in all layers (2.5:1; p<0.05), particularly in the adventitia (3.4:1; p<0.001). Microfibril-associated glycoprotein-1 (MAGP-1), which promotes TGFβ release, was elevated (2:1; p<0.03), while latent TGFβ binding protein-1 (LTBP-1), which promotes TGFβ sequestration, was decreased (0.3:1; p=0.03). Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was elevated (2.6:1; p<0.005, 1.5:1; p<0.05, respectively), and MMP-3 expression was decreased (0.5:1; p<0.05). Fibrillin-1 expression was not altered. The observed changes in TGFβ sequestration proteins will increase unbound TGFβ, leading to upregulation of downstream signalling. The elevated levels of MMP-2 and MMP-9 mediate pathological matrix remodelling, leading to aortic dilatation. The paradoxical decrease in MMP-3 may represent a compensatory mechanism that attempts to reduce overall pathological MMP activity, in order to limit damage to the aortic wall. In conclusion, in BAV-TAA excessive TGFβ signalling is potentiated by reduced TGFβ sequestration, causing extra-cellular matrix degradation by MMPs. This supports the rationale for the use of angiotensin II receptor blockers in BAV-TAA.

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

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.

Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients

Gene ◽  
2013 ◽  
Vol 524 (2) ◽  
pp. 304-308 ◽  
Author(s):  
María Martín ◽  
Irene A. Pichel ◽  
Juan P. Flórez Muñoz ◽  
Manuel Naves-Díaz ◽  
María Palacín ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Matrix Metalloproteinase ◽  
Bicuspid Aortic Valve ◽  
Transcriptional Activity ◽  
Matrix Metalloproteinase 1

scholarly journals Multimodal Assessment of Vascular and Ventricular Function in Children and Adults With Bicuspid Aortic Valve Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Constance G. Weismann ◽  
Sara Ljungberg ◽  
Anna Åkesson ◽  
J Hlebowicz
Keyword(s):  
Aortic Valve ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Diastolic Dysfunction ◽  
Bicuspid Aortic Valve ◽  
Aortic Stiffness ◽  
Wave Reflection ◽  
Pulse Wave ◽  
Aortic Distensibility ◽  
Cardiovascular Assessment

Background: Bicuspid aortic valve (BAV), the most common congenital cardiac anomaly, has been associated with an aortopathy, increased aortic stiffness and diastolic dysfunction. The involved mechanisms and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with a history of BAV.Methods: Multimodal cardiovascular assessment included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection [central (cAIx75) and peripheral (pAIx75) augmentation index corrected to a heart rate of 75/min, aging index (AI)], carotid-femoral pulse wave velocity [cfPWV], and endothelial function (EndoPAT). Multivariable linear regression and correlation analyses were performed.Results: We included 47 BAV patients and 84 controls (age 8–65 years). Ascending aortic stiffness, pulse wave reflection (cAIx75, pAIx75, and AI) and central blood pressure were significantly increased in patients with BAV. However, PWV, cIMT, and endothelial function were not significantly different from controls. BAV patients had marginally reduced diastolic (E': β = −1.5, p &lt; 0.001) but not systolic function compared to controls. Overall, all parameters of arterial stiffness had moderate-strong correlations with diastolic dysfunction and age. In the BAV group, ascending aortic distensibility had the strongest correlation with diastolic dysfunction.Conclusions: BAV is associated with increased proximal arterial stiffness and wave reflection. However, PWV and cIMT are not increased, and endothelial function is preserved. This suggests that the mechanism of arterial and cardiac stiffening is different from patients with acquired heart diseases.

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