scholarly journals MicroRNA-34c Inhibits Osteogenic Differentiation and Valvular Interstitial Cell Calcification via STC1-Mediated JNK Pathway in Calcific Aortic Valve Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Lieming Yang ◽  
Xinyuan Zhu ◽  
Yingying Ni ◽  
Dawei Wu ◽  
Yikui Tian ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Osteogenic Differentiation ◽  
Aortic Valve Disease ◽  
Interstitial Cell ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Jnk Pathway

scholarly journals Label-free optical biomarkers detect early calcific aortic valve disease in a wild-type mouse model

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ishita Tandon ◽  
Shelby Johns ◽  
Alan Woessner ◽  
Jessica Perez ◽  
Delaney Cross ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Early Detection ◽  
Mouse Model ◽  
Osteogenic Differentiation ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Label Free ◽  
Calcific Aortic Valve Disease ◽  
Collagen Remodeling ◽  
Positive Expression

Abstract Background Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a diet-based, non-genetically modified mouse model for early CAVD progression, and explored the utility of two-photon excited fluorescence (TPEF) microscopy for early detection of CAVD progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with the potential to correlate with multiple stages of CAVD pathophysiology including calcium deposition, collagen remodeling and osteogenic differentiation. Methods Twenty-week old C57BL/6J mice were fed either a control or pro-calcific diet for 16 weeks and monitored via echocardiography, histology, immunohistochemistry, and quantitative polarized light imaging. Additionally, TPEF imaging was used to quantify tissue autofluorescence (A) at 755 nm, 810 nm and 860 nm excitation, to calculate TPEF 755–860 ratio (A860/525/(A755/460 + A860/525)) and TPEF Collagen-Calcium ratio (A810/525/(A810/460 + A810/525)) in the murine valves. In a separate experiment, animals were fed the above diets till 28 weeks to assess for later-stage calcification. Results Pro-calcific mice showed evidence of lipid deposition at 4 weeks and calcification at 16 weeks at the valve commissures. The valves of pro-calcific mice also showed positive expression for markers of osteogenic differentiation, myofibroblast activation, proliferation, inflammatory cytokines and collagen remodeling. Pro-calcific mice exhibited lower TPEF autofluorescence ratios, at locations coincident with calcification, that correlated with increased collagen disorganization and positive expression of osteogenic markers. Additionally, locations with lower TPEF autofluorescence ratios at 4 and 16 weeks exhibited increased calcification at later 28-week timepoints. Conclusions This study suggests the potential of TPEF autofluorescence metrics to serve as a label-free tool for early detection and monitoring of CAVD pathophysiology.

scholarly journals 16 Investigating calcific aortic valve disease using novel immortalised sheep and rat valve interstitial cell lines

1997 ◽  
Author(s):  
Hiu-Gwen Tsang ◽  
Lin Cui ◽  
Colin Farquharson ◽  
Brendan M Corcoran ◽  
Kim M Summers ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Cell Lines ◽  
Aortic Valve Disease ◽  
Interstitial Cell ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease

Abstract 141: Bicuspid Aortic Valve Hemodynamic Abnormalities Promote Early Development of Calcific Aortic Valve Disease

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ling Sun ◽  
Santanu Chandra ◽  
Philippe Sucosky
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Osteogenic Differentiation ◽  
Bicuspid Aortic Valve ◽  
Aortic Valve Disease ◽  
Tissue Response ◽  
Valve Disease ◽  
Type I ◽  
Calcific Aortic Valve Disease ◽  
Congenital Cardiac Anomaly

INTRODUCTION: The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific aortic valve disease (CAVD). Although CAVD also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. While the accelerated calcification of BAV leaflets has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors. HYPOTHESIS: Supported by our previous work, which demonstrated the sensitivity of valve leaflets to the surrounding blood flow and associated wall-shear stress (WSS), we hypothesize that the abnormal WSS experienced by BAV leaflets contribute to CAVD development by promoting valvular inflammation, remodeling and osteogenic differentiation. OBJECTIVE: This study aims at comparing ex vivo the effects of TAV and BAV leaflet WSS on valvular pathogenesis. METHODS: The native, side-specific WSS experienced by TAV and type-I (i.e., fused and non-coronary) BAV leaflets were obtained computationally using fluid-structure interaction simulations. Fresh porcine leaflets were subjected for 48 hours to each of the three WSS conditions using a novel double-sided shear stress bioreactor. Tissue response was characterized via Western blot and immunohistochemistry in terms of markers of endothelial activation (VCAM-1, ICAM-1), paracrine expression (BMP-4), TGF-β/Wnt signaling pathways (TGF-β1, β-catenin), extracellular matrix remodeling (cathepsin L, MMP-2, MMP-9) and osteogenic differentiation (α-SMA, osteocalcin). RESULTS: No significant differences in VCAM-1 and ICAM-1 expressions were detected between tissue exposed to TAV and BAV WSS. While the native WSS experienced by the TAV and non-coronary BAV leaflets maintained tissue homeostasis, tissue exposure to the fused BAV leaflet WSS resulted in a significant pathological response marked by the upregulations of BMP-4, β-catenin, MMP-2 and osteocalcin expressions. CONCLUSION: This study demonstrates the pathological nature of the native BAV hemodynamics and confirms the higher susceptibility of the fused BAV leaflet to calcify. The results provide new insights into the hemodynamic theory of BAV calcification.

Cardamonin inhibits osteogenic differentiation of human valve interstitial cells and ameliorates aortic valve calcification via interfering NF-κB/NLRP3 inflammasome pathway

2021 ◽  
Author(s):  
Chunli wang ◽  
Yi Xia ◽  
Linghang Qu ◽  
Yanju Liu ◽  
Xianqiong Liu ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Osteogenic Differentiation ◽  
Nlrp3 Inflammasome ◽  
Aortic Valve Disease ◽  
Interstitial Cells ◽  
Valve Disease ◽  
Aortic Valve Calcification ◽  
Calcific Aortic Valve Disease ◽  
Valve Calcification ◽  
Valve Interstitial Cells

Cardamonin (CDM) is a natural chalcone with strong anti-inflammatory properties. Inflammation-induced osteogenic changes in valve interstitial cells (VICs) play crucial roles in the development of calcific aortic valve disease (CAVD),...

scholarly journals Asporin Reduces Adult Aortic Valve Interstitial Cell Mineralization Induced by Osteogenic Media and Wnt Signaling Manipulation In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Anisha Polley ◽  
Riffat Khanam ◽  
Arunima Sengupta ◽  
Santanu Chakraborty
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Interstitial Cell ◽  
Valve Disease ◽  
Periodontal Ligament Cells ◽  
Calcific Aortic Valve Disease ◽  
Disease Manifestation ◽  
Regulatory Pathways ◽  
Replacement Surgery

Worldwide, calcific aortic valve disease is one of the leading causes of morbidity and mortality among patients with cardiac abnormalities. Aortic valve mineralization and calcification are the key events of adult calcific aortic valve disease manifestation and functional insufficiency. Due to heavy mineralization and calcification, adult aortic valvular cusps show disorganized and dispersed stratification concomitant with deposition of calcific nodules with severely compromised adult valve function. Interestingly, shared gene regulatory pathways are identified between bone-forming cells and heart valve cells during development. Asporin, a small leucine-rich proteoglycan (43 kDa), acts to inhibit mineralization in periodontal ligament cells and is also detected in normal murine adult aortic valve leaflets with unknown function. Therefore, to understand the Asporin function in aortic cusp mineralization and calcification, adult avian aortic valvular interstitial cell culture system is established and osteogenesis has been induced in these cells successfully. Upon induction of osteogenesis, reduced expression of Asporin mRNA and increased expression of bone and osteogenesis markers are detected compared to cells maintained without osteogenic induction. Importantly, treatment with human recombinant Asporin protein reduces the mineralization level in osteogenic media-induced aortic valvular interstitial cells with the concomitant decreased level of Wnt/β-catenin signaling. Overall, all these data are highly indicative that Asporin might be a novel biomolecular target to treat patients of calcific aortic valve disease over current cusp replacement surgery.

scholarly journals Exploiting novel valve interstitial cell lines to study calcific aortic valve disease

2017 ◽  
Author(s):  
Hiu‑Gwen Tsang ◽  
Lin Cui ◽  
Colin Farquharson ◽  
Brendan Corcoran ◽  
Kim Summers ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Cell Lines ◽  
Aortic Valve Disease ◽  
Interstitial Cell ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease

scholarly journals Evogliptin Suppresses Calcific Aortic Valve Disease by Attenuating Inflammation, Fibrosis, and Calcification

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 57
Author(s):  
Bongkun Choi ◽  
Eun-Young Kim ◽  
Ji-Eun Kim ◽  
Soyoon Oh ◽  
Si-On Park ◽  
...  
Keyword(s):  
Animal Models ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Rabbit Model ◽  
Cytokine Expression ◽  
Rate Of Change ◽  
Valve Disease ◽  
High Cholesterol Diet ◽  
Calcific Aortic Valve Disease ◽  
Valvular Calcification

Calcific aortic valve disease (CAVD) accompanies inflammatory cell infiltration, fibrosis, and ultimately calcification of the valve leaflets. We previously demonstrated that dipeptidyl peptidase-4 (DPP-4) is responsible for the progression of aortic valvular calcification in CAVD animal models. As evogliptin, one of the DPP-4 inhibitors displays high specific accumulation in cardiac tissue, we here evaluated its therapeutic potency for attenuating valvular calcification in CAVD animal models. Evogliptin administration markedly reduced calcific deposition accompanied by a reduction in proinflammatory cytokine expression in endothelial nitric oxide synthase-deficient mice in vivo, and significantly ameliorated the mineralization of the primary human valvular interstitial cells (VICs), with a reduction in the mRNA expression of bone-associated and fibrosis-related genes in vitro. In addition, evogliptin ameliorated the rate of change in the transaortic peak velocity and mean pressure gradients in our rabbit model as assessed by echocardiography. Importantly, evogliptin administration in a rabbit model was found to suppress the effects of a high-cholesterol diet and of vitamin D2-driven fibrosis in association with a reduction in macrophage infiltration and calcific deposition in aortic valves. These results have indicated that evogliptin prohibits inflammatory cytokine expression, fibrosis, and calcification in a CAVD animal model, suggesting its potential as a selective therapeutic agent for the inhibition of valvular calcification during CAVD progression.

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