scholarly journals Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets

2021 ◽  
Vol 8 ◽  
Author(s):  
Joshua D. Hutcheson ◽  
Florian Schlotter ◽  
Michael D. Creager ◽  
Xiaoshuang Li ◽  
Tan Pham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Valve ◽  
Elastic Fibers ◽  
Valvular Interstitial Cells ◽  
Mechanical Stiffness ◽  
Regional Patterns ◽  
Dopachrome Tautomerase ◽  
Human Aortic Valve ◽  
Elastin Gene

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues.Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression.Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.

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 Elastin biology and tissue engineering with adult cells

2013 ◽  
Vol 4 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Cassandra B. Saitow ◽  
Steven G. Wise ◽  
Anthony S. Weiss ◽  
John J. Castellot ◽  
David L. Kaplan
Keyword(s):  
Tissue Engineering ◽  
Normal Development ◽  
Elastic Fiber ◽  
Elastic Fibers ◽  
Accessory Proteins ◽  
Engineering Research ◽  
Elastin Gene ◽  
Tissue Engineering Research ◽  
Adult Cells

AbstractThe inability of adult cells to produce well-organized, robust elastic fibers has long been a barrier to the successful engineering of certain tissues. In this review, we focus primarily on elastin with respect to tissue-engineered vascular substitutes. To understand elastin regulation during normal development, we describe the role of various elastic fiber accessory proteins. Biochemical pathways regulating expression of the elastin gene are addressed, with particular focus on tissue-engineering research using adult-derived cells.

scholarly journals The stretch responsive microRNA miR‐148a‐3p is a novel repressor of IKBKB , NF‐κB signaling, and inflammatory gene expression in human aortic valve cells

2015 ◽  
Vol 29 (5) ◽  
pp. 1859-1868 ◽  
Author(s):  
Vishal Patel ◽  
Katrina Carrion ◽  
Andrew Hollands ◽  
Andrew Hinton ◽  
Thomas Gallegos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Valve ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Human Aortic Valve

scholarly journals Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors

2005 ◽  
Vol 26 (13) ◽  
pp. 1333-1341 ◽  
Author(s):  
Olivier Fondard ◽  
Delphine Detaint ◽  
Bernard Iung ◽  
Christine Choqueux ◽  
Homa Adle-Biassette ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Matrix Metalloproteinases ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Tissue Inhibitors ◽  
Extracellular Matrix Remodelling ◽  
Human Aortic Valve

scholarly journals Augmented Osteogenic Responses in Human Aortic Valve Cells Exposed to oxLDL and TLR4 Agonist: A Mechanistic Role of Notch1 and NF-κB Interaction

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e95400 ◽  
Author(s):  
Qingchun Zeng ◽  
Rui Song ◽  
Lihua Ao ◽  
Dingli Xu ◽  
Neil Venardos ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Tlr4 Agonist ◽  
Human Aortic Valve

scholarly journals Role of Noncanonical Wnt Signaling Pathway in Human Aortic Valve Calcification

2017 ◽  
Vol 37 (3) ◽  
pp. 543-552 ◽  
Author(s):  
Isabella Albanese ◽  
Bin Yu ◽  
Hamood Al-Kindi ◽  
Bianca Barratt ◽  
Leah Ott ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Human Aortic Valve

Transforming growth factor-β1 promotes fibrosis but attenuates calcification of valvular tissue applied as a three-dimensional calcific aortic valve disease model

2020 ◽  
Vol 319 (5) ◽  
pp. H1123-H1141 ◽  
Author(s):  
Alexander Jenke ◽  
Julia Kistner ◽  
Sarah Saradar ◽  
Agunda Chekhoeva ◽  
Mariam Yazdanyar ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Transforming Growth Factor ◽  
Disease Model ◽  
Three Dimensional ◽  
Valve Disease ◽  
Valvular Interstitial Cells ◽  
Calcific Aortic Valve Disease ◽  
Tgf Β1

Employing aortic valve leaflets as a tissue-based three-dimensional disease model, our study investigates the role of transforming growth factor (TGF)-β1 in calcific aortic valve disease pathogenesis. We find that, by activating Mothers against decapentaplegic homolog 3, TGF-β1 intensifies expressional and proliferative activation along with myofibroblastic differentiation of valvular interstitial cells, thus triggering dominant fibrosis. Simultaneously, by inhibiting activation of Mothers against decapentaplegic homolog 1/5/8 and canonical Wnt/β-catenin signaling, TGF-β1 attenuates apoptosis and osteoblastic differentiation of valvular interstitial cells, thus blocking valvular tissue calcification. These findings question a general phase-independent calcific aortic valve disease-promoting role of TGF-β1.

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