scholarly journals Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells

2019 ◽  
Vol 20 (6) ◽  
pp. 1486 ◽  
Author(s):  
Miguel Carracedo ◽  
Oscar Persson ◽  
Peter Saliba-Gustafsson ◽  
Gonzalo Artiach ◽  
Ewa Ehrenborg ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Interstitial Cells ◽  
Left Ventricular ◽  
Autophagic Flux ◽  
Valvular Interstitial Cells ◽  
Survival Mechanism ◽  
Calcified Tissue ◽  
Left Ventricular Outflow

Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.

scholarly journals Congenital Aortic Valve Stenosis

Children ◽  
2019 ◽  
Vol 6 (5) ◽  
pp. 69 ◽  
Author(s):  
Gautam K. Singh
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Left Ventricular Outflow Tract ◽  
Significant Risk ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Outflow Tract ◽  
Ventricular Outflow Tract Obstruction ◽  
Young Infants ◽  
Left Ventricular Outflow

Aortic valve stenosis in children is a congenital heart defect that causes fixed form of hemodynamically significant left ventricular outflow tract obstruction with progressive course. Neonates and young infants who have aortic valve stenosis, usually develop congestive heart failure. Children and adolescents who have aortic valve stenosis, are mostly asymptomatic, although they may carry a small but significant risk of sudden death. Transcatheter or surgical intervention is indicated for symptomatic patients or those with moderate to severe left ventricular outflow tract obstruction. Many may need reintervention.

scholarly journals Genetic testing for aortic valve stenosis

2018 ◽  
Vol 2 (s1) ◽  
pp. 61-63
Author(s):  
Yeltay Rakhmanov ◽  
Paolo Enrico Maltese ◽  
Alessandra Zulian ◽  
Stefano Paolacci ◽  
Tommaso Beccari ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Differential Diagnosis ◽  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Autosomal Dominant ◽  
Left Ventricular ◽  
Dominant Inheritance ◽  
Gene Test ◽  
Left Ventricular Outflow

Abstract Aortic valve stenosis (AVS) is a congenital aortic defect in which the aortic lumen narrows due to thickening or calcification of the aortic valve without obstructing left ventricular outflow. Depending on the site of obstruction, AVS is classified as valvular, sub-valvular or supra-valvular. The prevalence of AVS is about 3% and increases with age. One in eight persons over the age of 75 years has moderate or severe AVS. AVS has autosomal dominant inheritance. It can be associated with mutations in the following genes: NOTCH1, SMAD6, SMAD4, and ELN. This Utility Gene Test was developed on the basis of the analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials, when available.

Abstract 288: Mice With Disruptive Egfr Signaling In The Aortic Valves Develop Calcific Aortic Valve Stenosis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Bin Zhou ◽  
Bingruo Wu
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Clinical Importance ◽  
Interstitial Cells ◽  
Left Ventricular ◽  
Specific Gene ◽  
Egfr Signaling ◽  
Aortic Valves ◽  
Major Health Problem ◽  
Mesenchymal Transition

Calcific aortic valve stenosis is a major health problem. Despite its clinical importance, the pathogenesis of this condition remains illusive. Aortic valves are made of endothelial cells and interstitial cells, both are derived from the endocardial cells of the heart during development. We have developed a new mouse model, Nfatc1-Cre, to specifically study the biology of the valve cells during valve development. In this study, we deleted epidermal growth factor receptor (Egfr) in the aortic valves using the Nfatc1-Cre and showed by histological and biochemical analyses that this deletion caused a spectrum of pathological characteristics of human calcific aortic valve stenosis. They include increased proliferation and dedifferentiation of the valve interstitial cells, abnormal deposition of extracellular matrix, bone-like formation and calcification. The null mice eventually developed the left ventricular dysfunction, presumably secondary to the stenotic aortic valves. We also revealed by immunohistochemistry and quantitative RT-PCR the changes in gene expression involved in the epithelial-to-mesenchymal transition or osteogenic activities. Altogether, these results demonstrate that Egfr signaling in the valve endothelial and interstitial cells regulates the homeostasis of the aortic valves and suggest that patients with mutations or medications affecting the Egfr signaling may be at the risk to develop calcific aortic valve stenosis. Our study also provides the proof-of-principle data showing that the Nfatc1-Cre is a useful genetic tool to elucidate the valve-specific gene function involved in the valve homeostasis and disease.

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