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.

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 How to approach aortic valve disease in the elderly : a 25-year retrospective study : cardiovascular topic

2014 ◽  
Vol 25 (5) ◽  
pp. 244-248 ◽  
Author(s):  
Ebuzer Aydin ◽  
Ozge Altas Yerlikhan ◽  
Behzat Tuzun ◽  
Yucel Ozen ◽  
Sabit Sarikaya ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
The Elderly ◽  
Valve Disease

Abstract P098: Inhibitory Role of Notch1 in Calcific Aortic Valve Disease Is Mediated by Sox9

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Chetan P Hans ◽  
Asha Acharya ◽  
Sara N Koenig ◽  
Haley A Nichols ◽  
Cristi L Galindo ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Aortic Valve Disease ◽  
Notch Signaling Pathway ◽  
Valve Disease ◽  
Calcium Deposition ◽  
Aortic Valve Calcification ◽  
Calcific Aortic Valve Disease ◽  
Valve Calcification

Introduction: Aortic valve calcification is the most common form of valvular heart disease; however the mechanism(s) underlying calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. Objective: To investigate the molecular changes associated with the calcification of aortic valve that occurs with inhibition of Notch signaling. Methods and Results: The expression of Notch signaling pathway members was validated in the aortic valve cusps from adult mice, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1 signaling, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of many cartilage-specific genes that constitute the valve extracellular matrix (ECM). Analysis of these cartilage-specific genes demonstrated that several were transcriptional targets of Sox9, a master regulator of chondrogenesis, which has been previously shown to be essential for proper valve development and maintenance. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, utilizing transfection studies, addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. Conclusions: Loss of Notch signaling contributes to aortic valve calcification by a Sox9-dependent mechanism. Further elucidation of the Notch1-Sox9 molecular pathway and its role in the maintenance of the ECM will lead to an improved mechanistic understanding of aortic valve calcification and development of novel therapeutic strategies for CAVD.

Aortic Valvular Disease

2019 ◽  
pp. 385-414
Author(s):  
Eric Leo Sarin ◽  
Vinod H. Thourani
Keyword(s):  
United States ◽  
Aortic Valve ◽  
Life Expectancy ◽  
Elderly Patients ◽  
Aortic Valve Disease ◽  
The Elderly ◽  
The United States ◽  
Degenerative Disease ◽  
Valve Disease ◽  
Valvular Stenosis

Broadly speaking, pathology is categorized as being primarily related to valvular stenosis (AS) or regurgitation (AR), but a diseased valve may often exhibit both. The predilection of degenerative disease of the aortic valve, particularly stenosis, for the elderly has resulted in a steadily increasing prevalence as the population ages. As general life expectancy increases in the United States and other western countries, surgery to correct aortic valve disease will increase. As more elderly patients with more comorbidities present for surgery their intraoperative and perioperative care will become more complex. This chapter discusses ways for the practicing intensivist to facilitate identification and treatment in the immediate peri-operative period.

scholarly journals Risk Factors for Progression of Degenerative Aortic Valve Disease in the Japanese　– The Japanese Aortic Stenosis Study (JASS) Prospective Analysis –

2015 ◽  
Vol 79 (9) ◽  
pp. 2050-2057 ◽  
Author(s):  
Kazuhiro Yamamoto ◽  
Hideya Yamamoto ◽  
Masaaki Takeuchi ◽  
Akira Kisanuki ◽  
Takashi Akasaka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Prospective Analysis

Surgical Management of Aortic Valve Disease in the Elderly: A Longitudinal Analysis

1988 ◽  
Vol 46 (3) ◽  
pp. 264-269 ◽  
Author(s):  
Luis N. Bessone ◽  
Dennis F. Pupello ◽  
Stephen P. Hiro ◽  
Enrique Lopez-Cuenca ◽  
M.S. Glatterer ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Surgical Management ◽  
Longitudinal Analysis ◽  
Aortic Valve Disease ◽  
The Elderly ◽  
Valve Disease
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