scholarly journals Sex-Specific Features of Calcific Aortic Valve Disease

2020 ◽  
Vol 21 (16) ◽  
pp. 5620 ◽  
Author(s):  
Volha I. Summerhill ◽  
Donato Moschetta ◽  
Alexander N. Orekhov ◽  
Paolo Poggio ◽  
Veronika A. Myasoedova
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Disease ◽  
The Elderly ◽  
Developed Countries ◽  
Left Ventricular ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Men And Women ◽  
Increased Risk

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a gradually progressive condition ranging from mild valve calcification and thickening, without the hemodynamic obstruction, to severe calcification impairing leaflet motion, known as aortic stenosis (AS). The progression of CAVD occurs over many years, and it is extremely variable among individuals. It is also associated with an increased risk of coronary events and mortality. The recent insights into the CAVD pathophysiology included an important role of sex. Accumulating evidence suggests that, in patients with CAVD, sex can determine important differences in the relationship between valvular calcification process, fibrosis, and aortic stenosis hemodynamic severity between men and women. Consequently, it has implications on the development of different valvular phenotypes, left ventricular hypertrophy, and cardiovascular outcomes in men and women. Along these lines, taking into account the sex-related differences in diagnosis, prognosis, and treatment outcomes is of profound importance. In this review, the sex-related differences in patients with CAVD, in terms of pathobiology, clinical phenotypes, and outcomes were discussed.

scholarly journals Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers

2021 ◽  
Vol 22 (7) ◽  
pp. 3569
Author(s):  
Beau Olivier van van Driel ◽  
Maike Schuldt ◽  
Sila Algül ◽  
Evgeni Levin ◽  
Ahmet Güclü ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Surgery ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Western Blot ◽  
Aortic Valve Disease ◽  
Metabolic Profile ◽  
Valve Disease ◽  
Healthy Controls ◽  
Calcific Aortic Valve Disease

Background: Calcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve. AS is underdiagnosed, and if treatment by aortic valve replacement (AVR) is delayed, this leads to poor recovery of cardiac function, absence of symptomatic improvement and marked increase of mortality. Considering the current limitations to define the stage of AS-induced cardiac remodeling, there is need for a novel method to aid in the diagnosis of AS and timing of intervention, which may be found in metabolomics profiling of patients. Methods: Serum samples of nine healthy controls and 10 AS patients before and after AVR were analyzed by untargeted mass spectrometry. Multivariate modeling was performed to determine a metabolic profile of 30 serum metabolites which distinguishes AS patients from controls. Human cardiac microvascular endothelial cells (CMECs) were incubated with serum of the AS patients and then stained for ICAM-1 with Western Blot to analyze the effect of AS patient serum on endothelial cell activation. Results: The top 30 metabolic profile strongly distinguishes AS patients from healthy controls and includes 17 metabolites related to nitric oxide metabolism and 12 metabolites related to inflammation, in line with the known pathomechanism for calcific aortic valve disease. Nine metabolites correlate strongly with left ventricular mass, of which three show reversal back to control values after AVR. Western blot analysis of CMECs incubated with AS patient sera shows a significant reduction (14%) in ICAM-1 in AS samples taken after AVR compared to AS patient sera before AVR. Conclusion: Our study defined a top 30 metabolic profile with biological and clinical relevance, which may be used as blood biomarker to identify AS patients in need of cardiac surgery. Future studies are warranted in patients with mild-to-moderate AS to determine if these metabolites reflect disease severity and can be used to identify AS patients in need of cardiac surgery.

scholarly journals Extracellular Matrix in Calcific Aortic Valve Disease: Architecture, Dynamic and Perspectives

2021 ◽  
Vol 22 (2) ◽  
pp. 913
Author(s):  
Anna Di Vito ◽  
Annalidia Donato ◽  
Ivan Presta ◽  
Teresa Mancuso ◽  
Francesco Saverio Brunetti ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Matrix Vesicles ◽  
Developed Countries ◽  
Valve Disease ◽  
Ageing Population ◽  
Calcific Aortic Valve Disease ◽  
Molecular Alterations ◽  
Active Processes

Calcific Aortic Valve Disease (CAVD) is the most common valvular heart disease in developed countries and in the ageing population. It is strongly correlated to median age, affecting up to 13% of the population over the age of 65. Pathophysiological analysis indicates CAVD as a result of an active and degenerative disease, starting with sclerosis and chronic inflammation and then leaflet calcification, which ultimately can account for aortic stenosis. Although CAVD has been firstly recognized as a passive event mostly resulting from a degenerative aging process, much evidences suggests that calcification arises from different active processes, involving both aortic valve-resident cells (valve endothelial cells, valve interstitial cells, mesenchymal stem cells, innate immunity cells) and circulating cells (circulating mesenchymal cells, immunity cells). Moreover, a role for the cell-derived “matrix vesicles” and extracellular matrix (ECM) components has also been recognized. The aim of this work is to review the cellular and molecular alterations occurring in aortic valve during CAVD pathogenesis, focusing on the role of ECM in the natural course of the disease.

scholarly journals Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Petra Büttner ◽  
Lukas Feistner ◽  
Philipp Lurz ◽  
Holger Thiele ◽  
Joshua D. Hutcheson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Molecular Mechanisms ◽  
Left Ventricular ◽  
Valve Disease ◽  
Reverse Remodeling ◽  
Calcific Aortic Valve Disease ◽  
Ecm Remodeling ◽  
The Individual

Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.

Structural Deformation of Native Aortic Valve Leaflet Under Hypertension: An In Vitro Study

2009 ◽  
Author(s):  
C. H. Yap ◽  
H. S. Kim ◽  
L. P. Dasi ◽  
M. J. Weiler ◽  
K. Balachandran ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Fluid Shear Stress ◽  
Complex Structure ◽  
Valve Disease ◽  
Structural Deformation ◽  
Fluid Shear ◽  
Calcific Aortic Valve Disease ◽  
Increased Risk

The aortic valve (AV) is a complex structure that functions in a complex dynamic environment. During systole, the valve leaflets bend at the base to open and experience fluid shear stress on both ventricular and aortic sides of the leaflet. During diastole, adverse pressure gradient closes the valve causing it to structurally support the systemic afterload pressure. Ex vivo experiments has shown that isolated mechanical forces such as pressure, membrane tension, and fluid shear stress affects the remodeling activities of the valve leaflets and also elicit pathological responses [1], potentially leading to calcific aortic valve disease in the long term. Clinically, patients with hypertension have increased risk of developing calcific aortic valve disease [2], which could be a result of the increased pressure or the increased stretch on the valve leaflets.

scholarly journals Valvular Aortic Stenosis: A Proteomic Insight

2010 ◽  
Vol 4 ◽  
pp. CMC.S3884 ◽  
Author(s):  
Felix Gil-Dones ◽  
Tatiana Martin-Rojas ◽  
Luis F. Lopez-Almodovar ◽  
Fernando De La Cuesta ◽  
Veronica M. Darde ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Disease ◽  
Protein Extraction ◽  
Protein Profile ◽  
The Elderly ◽  
Valve Disease ◽  
Calcium Deposition ◽  
2D Dige ◽  
High Calcium

Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area. Until recently, aortic stenosis (AS) was considered a passive process secondary to calcium deposition in the aortic valves. However, it has recently been highlighted that the risk factors associated with the development of calcified AS in the elderly are similar to those of coronary artery disease. Furthermore, degenerative AS shares histological characteristics with atherosclerotic plaques, leading to the suggestion that calcified aortic valve disease is a chronic inflammatory process similar to atherosclerosis. Nevertheless, certain data does not fit with this theory making it necessary to further study this pathology. The aim of this study is to develop an effective protein extraction protocol for aortic stenosis valves such that proteomic analyses can be performed on these structures. In the present work we have defined a rapid, reproducible and effective method to extract proteins and that is compatible with 2-DE, 2D-DIGE and MS techniques. Defining the protein profile of this tissue is an important and challenging task that will help to understand the mechanisms of physiological/pathological processes in aortic stenosis valves.

Ventricular mechanics in patients with aortic valve disease: longitudinal, radial, and circumferential components

2013 ◽  
Vol 24 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Benedetta Leonardi ◽  
Renee Margossian ◽  
Stephen P. Sanders ◽  
Marcello Chinali ◽  
Steven D. Colan
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Regurgitation ◽  
Aortic Valve Disease ◽  
Longitudinal Strain ◽  
Circumferential Strain ◽  
Wall Stress ◽  
Left Ventricular ◽  
Valve Disease ◽  
Mass Volume

AbstractBackgroundReduced long-axis shortening despite enhanced global function has been reported in aortic stenosis. We sought to improve the understanding of this phenomenon using multi-dimensional strain analysis in conjunction with the evaluation of left ventricular rotation and twist – ventricular torsion – using tissue Doppler techniques.MethodsA total of 57 patients with variable severity of aortic stenosis, aortic regurgitation, or mixed aortic valve disease, subdivided into six groups, were studied. Ventricular morphology was assessed using long-axis/short-axis and mass/volume ratios, afterload using end-systolic meridional wall stress, and global performance using ejection fraction. The circumferential and longitudinal strain was measured from two-dimensional images, and left ventricular rotation and twist were estimated as the difference in rotation between the base and apex of the ventricle.ResultsAortic stenosis was associated with higher mass/volume, ejection fraction, circumferential strain and left ventricular rotation and twist, significantly lower end-systolic wall stress, and a trend towards lower longitudinal strain compared with normal. Myocardial mechanics in aortic regurgitation were normal despite ventricular dilation. Mixed aortic valve disease showed findings similar to aortic stenosis. Left ventricular rotation and twist correlated with midwall circumferential strain (r = 0.62 and p < 0.0001), endocardial circumferential strain (r = 0.61 and p < 0.0001), and end-systolic wall stress (r = 0.48 and p < 0.0001), but not with longitudinal strain (r = 0.18 and p > 0.05).ConclusionsMyocardial mechanics are normal in patients with aortic regurgitation, independent of abnormalities in cardiac geometry. Conversely, in aortic stenosis and mixed aortic valve disease, significant alterations in the patterns of fibre shortening are found. The effects of stenosis on cardiac function seem to dominate the effect of ventricular remodelling.

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