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https://www.readbyqxmd.com/read/29847020/warfarin-but-not-rivaroxaban-promotes-the-calcification-of-the-aortic-valve-in-apoe-mice
#1
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Chiara Nardin, Leopoldo Pagliani, Mario Plebani, Francesco Cinetto, Diego Guidolin, Massimo Puato, Paolo Pauletto
INTRODUCTION: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification. AIMS: to compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice...
May 30, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29804152/probing-the-effect-of-morphology-on-lymphatic-valve-dynamic-function
#2
Matthew Ballard, Ki T Wolf, Zhanna Nepiyushchikh, J Brandon Dixon, Alexander Alexeev
The lymphatic system is vital to the circulatory and immune systems, performing a range of important functions such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels are composed of contractile walls and lymphatic valves, allowing them to pump lymph against adverse pressure gradients and to prevent backflow. Despite the importance of the lymphatic system, the contribution of mechanical and geometric changes of lymphatic valves and vessels in pathologies of lymphatic dysfunction, such as lymphedema, is not well understood...
May 26, 2018: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/29777507/rankl-expression-is-increased-in-circulating-mononuclear-cells-of-patients-with-calcific-aortic-stenosis
#3
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Roberta Buso, Massimo Puato, Mario Plebani, Martina Zaninotto, Davide Condotta, Giacomo Zoppellaro, Leopoldo Pagliani, Giuseppe Tarantini, Sabino Iliceto, Elisa Covolo, Giuseppe Faggian, Francesco Onorati, Mikhail Dodonov, Alessandro Daniotti, Paola Pantano, Zoran Olivari, Giovanni Benfari, Paolo Pauletto
We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0...
May 17, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29761409/the-roles-of-matrix-stiffness-and-%C3%A3-catenin-signaling-in-endothelial-to-mesenchymal-transition-of-aortic-valve-endothelial-cells
#4
Aileen Zhong, Zahra Mirzaei, Craig A Simmons
Valve stiffening is a hallmark of aortic valve stenosis caused by excess extracellular matrix accumulation by myofibroblasts. We aimed to elucidate whether matrix stiffness regulates endothelial-to-mesenchymal transition (EndMT) of adult valvular endothelial cells (VECs) to myofibroblasts as a mechanism to further promote valve fibrosis. In addition, we specifically examined the role of the Wnt/β-catenin signaling pathway in the development of myofibroblasts during EndMT, as Wnt/β-catenin signaling has been implicated in EndMT during heart development, is reactivated in valve disease, and is required for mechanically-regulated myofibrogenesis of valve interstitial cells...
May 14, 2018: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/29751516/engineering-a-3d-bioprinted-model-of-human-heart-valve-disease-using-nanoindentation-based-biomechanics
#5
Dewy C van der Valk, Casper F T van der Ven, Mark C Blaser, Joshua M Grolman, Pin-Jou Wu, Owen S Fenton, Lang H Lee, Mark W Tibbitt, Jason L Andresen, Jennifer R Wen, Anna H Ha, Fabrizio Buffolo, Alain van Mil, Carlijn V C Bouten, Simon C Body, David J Mooney, Joost P G Sluijter, Masanori Aikawa, Jesper Hjortnaes, Robert Langer, Elena Aikawa
In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time...
May 3, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29749108/biomaterial-characterization-of-off-the-shelf-decellularized-porcine-pericardial-tissue-for-use-in-prosthetic-valvular-applications
#6
Joshua A Choe, Soumen Jana, Brandon J Tefft, Ryan S Hennessy, Jason Go, David Morse, Amir Lerman, Melissa D Young
Fixed pericardial tissue is commonly used for commercially available xenograft valve implants, and has proven durability, but lacks the capability to remodel and grow. Decellularized porcine pericardial tissue has the promise to outperform fixed tissue and remodel, but the decellularization process has been shown to damage the collagen structure and reduce mechanical integrity of the tissue. Therefore, a comparison of uniaxial tensile properties was performed on decellularized, decellularized-sterilized, fixed, and native porcine pericardial tissue, versus native valve leaflet cusps...
May 10, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29748157/interleukin-32-plays-an-essential-role-in-human-calcified-aortic-valve-cells
#7
Chung-Lin Tsai, Ying-Ming Chiu, Yi-Ju Lee, Chin-Tung Hsieh, Dong-Chen Shieh, Gregory J Tsay, Da-Tian Bau, Yi-Ying Wu
Interleukin-32 (IL-32) is an inflammatory cytokine produced mainly by T, natural killer, and epithelial cells. Previous studies on IL-32 have primarily investigated its proinflammatory properties. The IL-32 also has been described as an activator of the p38 mitogen-activated protein kinase (MAPK) and NF-κB, and induces several cytokines. In this study, we hypothesized that the inflammatory regulators NF-κB, MAP kinase, STAT1, and STAT3 are associated with the expression of the IL-32 protein in human calcified aortic valve cells...
March 1, 2018: European Cytokine Network
https://www.readbyqxmd.com/read/29729718/development-and-evaluation-of-a-tissue-engineered-fibrin-based-canine-mitral-valve-three-dimensional-cell-culture-system
#8
M-M Liu, T C Flanagan, S Jockenhovel, A Black, C-C Lu, A T French, D J Argyle, B M Corcoran
Myxomatous mitral valve disease is the most common cardiac disease of the dog, but examination of the associated cellular and molecular events has relied on the use of cadaveric valve tissue, in which functional studies cannot be undertaken. The aim of this study was to develop a three-dimensional (3D) cell co-culture model as an experimental platform to examine disease pathogenesis. Mitral valve interstitial (VIC) and endothelial (VEC) cells were cultured from normal and diseased canine (VIC only) valves. VICs were embedded in a fibrin-based hydrogel matrix and one surface was lined with VECs...
April 2018: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/29726894/dna-methylation-of-a-plpp3-mir-transposon-based-enhancer-promotes-an-osteogenic-program-in-calcific-aortic-valve-disease
#9
Ghada Mkannez, Valérie Gagné-Ouellet, Mohamed Jalloul Nsaibia, Marie-Chloé Boulanger, Mickael Rosa, Deborah Argaud, Fayez Hadji, Nathalie Gaudreault, Gabrielle Rhéaume, Luigi Bouchard, Yohan Bossé, Patrick Mathieu
Aims: Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD. Methods and Results: The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs...
May 2, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29713107/lymphatic-system-flows
#10
James E Moore, Christopher D Bertram
The supply of oxygen and nutrients to tissues is performed by the blood system, and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH2 O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls...
January 2018: Annual Review of Fluid Mechanics
https://www.readbyqxmd.com/read/29694513/mir-27a-protects-human-mitral-valve-interstitial-cell-from-tnf-%C3%AE-induced-inflammatory-injury-via-up-regulation-of-nell-1
#11
Honglei Chen, Zhixu Zhang, Li Zhang, Junzhi Wang, Minghui Zhang, Bin Zhu
MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29679571/metformin-ameliorates-tgf-%C3%AE-1-induced-osteoblastic-differentiation-of-human-aortic-valve-interstitial-cells-by-inhibiting-%C3%AE-catenin-signaling
#12
Fayuan Liu, Chong Chu, Qinyu Wei, Jiawei Shi, Huadong Li, Nianguo Dong
Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-β1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29618659/mesenchymal-tnfr2-promotes-the-development-of-polyarthritis-and-comorbid-heart-valve-stenosis
#13
Maria Sakkou, Panagiotis Chouvardas, Lydia Ntari, Alejandro Prados, Kristin Moreth, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Maria C Denis, Niki Karagianni, George Kollias
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in arthritis has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific role of Tnfr2 in the TnfΔARE mouse model of SpA in arthritis and heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 signaling in resident synovial fibroblasts (SFs) and valvular interstitial cells (VICs) is detrimental for both pathologies, pointing to common cellular mechanisms...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29614432/pathological-significance-of-lipoprotein-a-in-aortic-valve-stenosis
#14
Bin Yu, Kashif Khan, Qutayba Hamid, Ahmad Mardini, Ateeque Siddique, Louis Philippe Aguilar-Gonzalez, Georges Makhoul, Hossny Alaws, Jacques Genest, George Thanassoulis, Renzo Cecere, Adel Schwertani
BACKGROUND AND AIMS: Aortic valve stenosis (AVS) affects a significant percentage of our elderly population and younger subjects with familial hypercholesterolemia. Lipoprotein(a) [Lp(a)] has been associated with AVS in recent genetic studies. The purpose of this study was to determine the effects of Lp(a) on human aortic valve interstitial cells (HAVICs), and to identify apolipoproteins and phospholipids in diseased human aortic valves. METHODS: We examined the effects of Lp(a) on HAVICs mineralization and oxidant formation...
May 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29594151/advances-in-pathophysiology-of-calcific-aortic-valve-disease-propose-novel-molecular-therapeutic-targets
#15
Alexia Hulin, Alexandre Hego, Patrizio Lancellotti, Cécile Oury
Calcific Aortic Valve Disease (CAVD) is the most common heart valve disease and its incidence is expected to rise with aging population. No medical treatment so far has shown slowing progression of CAVD progression. Surgery remains to this day the only way to treat it. Effective drug therapy can only be achieved through a better insight into the pathogenic mechanisms underlying CAVD. The cellular and molecular events leading to leaflets calcification are complex. Upon endothelium cell damage, oxidized LDLs trigger a proinflammatory response disrupting healthy cross-talk between valve endothelial and interstitial cells...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29592957/intra-cardiac-release-of-extracellular-vesicles-shapes-inflammation-following-myocardial-infarction
#16
Xavier Loyer, Ivana Zlatanova, Cécile Devue, Min Yin, Kiave-Yune Howangyin, Phatchanat Klaihmon, Coralie L Guerin, Marouane Kheloufi, José Vilar, Konstantinos Zannis, Bernd K Fleischmann, Do Won Hwang, Jongmin Park, Hakho Lee, Philippe Menasche, Jean-Sébastien Silvestre, Chantal M Boulanger
<u>Rationale:</u> A rapid and massive influx of inflammatory cells occurs into ischemic area following myocardial infarction, resulting in local release of cytokines and growth factors. Yet, the mechanisms regulating their production are not fully explored. The release of extracellular vesicles (EV) in the interstitial space curbs important biological functions, including inflammation, and influences the development of cardiovascular diseases. So far, there is no evidence for in situ release of cardiac EVs following myocardial infarction...
March 28, 2018: Circulation Research
https://www.readbyqxmd.com/read/29588317/spatiotemporal-multi-omics-mapping-generates-a-molecular-atlas-of-the-aortic-valve-and-reveals-networks-driving-disease
#17
Florian Schlotter, Arda Halu, Shinji Goto, Mark C Blaser, Simon C Body, Lang H Lee, Hideyuki Higashi, Daniel M DeLaughter, Joshua D Hutcheson, Payal Vyas, Tan Pham, Maximillian A Rogers, Amitabh Sharma, Christine E Seidman, Joseph Loscalzo, Jonathan G Seidman, Masanori Aikawa, Sasha A Singh, Elena Aikawa
Background -No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive valve replacement. The search for therapeutics and early diagnostics is challenging since CAVD presents in multiple pathological stages. Moreover, it occurs in the context of a complex, multi-layered tissue architecture, a rich and abundant extracellular matrix phenotype, and a unique, highly plastic and multipotent resident cell population. Methods -A total of 25 human stenotic aortic valves obtained from valve replacement surgeries were analyzed by multiple modalities, including transcriptomics and global unlabeled and label-based tandem-mass-tagged proteomics...
March 27, 2018: Circulation
https://www.readbyqxmd.com/read/29558203/enzymes-of-the-purinergic-signaling-system-exhibit-diverse-effects-on-the-degeneration-of-valvular-interstitial-cells-in-a-3-d-microenvironment
#18
Andreas Weber, Mareike Barth, Jessica Isabel Selig, Silja Raschke, Konstantinos Dakaras, Alexander Hof, Julia Hesse, Jürgen Schrader, Artur Lichtenberg, Payam Akhyari
Calcific aortic valve disease is an active disease process with lipoprotein deposition, chronic inflammation, and progressive leaflet degeneration. Expression of ectonucleotidases, a group of membrane-bound enzymes that regulate the metabolism of ATP and its metabolites, may coregulate the degeneration process of valvular interstitial cells (VICs). The aim of this study was to investigate the role of the enzymes of the purinergic system in the degeneration process of VICs. Ovine VICs were cultivated in vitro under different prodegenerative conditions and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39)/ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5'-nucleotidase (CD73), as well as with adenosine and adenosine receptor agonists...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29539583/increased-calcific-aortic-valve-disease-in-response-to-a-diabetogenic-procalcific-diet-in-the-ldlr-apob-100-100-mouse-model
#19
Marta Scatena, Melissa F Jackson, Mei Y Speer, Elizabeth M Leaf, Mary C Wallingford, Cecilia M Giachelli
OBJECTIVE: Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis (AS) and cardiac insufficiency. Patients with type II diabetes mellitus (T2DM) are at heightened risk for CAVD, and their valves have greater calcification than nondiabetic valves. No drugs to prevent or treat CAVD exist, and animal models that might help identify therapeutic targets are sorely lacking. To develop an animal model mimicking the structural and functional features of CAVD in people with T2DM, we tested a diabetogenic, procalcific diet and its effect on the incidence and severity of CAVD and AS in the, LDLr-/- ApoB100/100 mouse model...
May 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29505894/human-ipsc-derived-mesenchymal-stem-cells-encapsulated-in-pegda-hydrogels-mature-into-valve-interstitial-like-cells
#20
Aline L Y Nachlas, Siyi Li, Rajneesh Jha, Monalisa Singh, Chunhui Xu, Michael E Davis
Despite recent advances in tissue engineered heart valves (TEHV), a major challenge is identifying a cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. This study demonstrates that induced pluripotent stem cells (iPSC)-derived mesenchymal stem cells (iMSCs) can be derived from iPSCs using a feeder-free protocol and then further matured into VICs by encapsulation within 3D hydrogels...
April 15, 2018: Acta Biomaterialia
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