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https://www.readbyqxmd.com/read/28429161/on-the-in-vivo-function-of-the-mitral-heart-valve-leaflet-insights-into-tissue-interstitial-cell-biomechanical-coupling
#1
Chung-Hao Lee, Will Zhang, Kristen Feaver, Robert C Gorman, Joseph H Gorman, Michael S Sacks
There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states...
April 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28396860/aortic-valve-replacement-for-moderate-aortic-stenosis-with-severe-calcification-and-left-ventricualr-dysfunction-a-case-report-and-review-of-the-literature
#2
Nikhil Narang, Roberto M Lang, Vladimir M Liarski, Valluvan Jeevanandam, Marion A Hofmann Bowman
A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28390245/myofibroblastic-activation-of-valvular-interstitial-cells-is-modulated-by-spatial-variations-in-matrix-elasticity-and-its-organization
#3
Hao Ma, Anouk R Killaars, Frank W DelRio, Chun Yang, Kristi S Anseth
Valvular interstitial cells (VICs) are key regulators of the heart valve's extracellular matrix (ECM), and upon tissue damage, quiescent VIC fibroblasts become activated to myofibroblasts. As the behavior of VICs during disease progression and wound healing is different compared to healthy tissue, we hypothesized that the organization of the matrix mechanics, which results from depositing of collagen fibers, would affect VIC phenotypic transition. Specifically, we investigated how the subcellular organization of ECM mechanical properties affects subcellular localization of Yes-associated protein (YAP), an early marker of mechanotransduction, and α-smooth muscle actin (α-SMA), a myofibroblast marker, in VICs...
March 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/28377507/an-epigenetic-regulatory-loop-controls-pro-osteogenic-activation-by-tgf-%C3%AE-1-or-bone-morphogenetic-protein-2-in-human-aortic-valve-interstitial-cells
#4
Rui Song, David A Fullerton, Lihua Ao, Ke-Seng Zhao, Xianzhong Meng
Calcific aortic valve disease (CAVD) is common in the elderly population, but pharmacological interventions for managing valvular calcification are unavailable. Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) induce pro-osteogenic activation of human aortic valve interstitial cells (AVICs) that play an important role in valvular calcification. However, the molecular mechanism underlying pro-osteogenic activation in AVICs is incompletely understood. Here, we investigated an epigenetic regulatory mechanism in human AVIC pro-osteogenic activation induced by TGF-β1 and BMP-2...
April 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28369848/end-stage-renal-disease-induced-hypercalcemia-may-promote-aortic-valve-calcification-via-annexin-vi-enrichment-of-valve-interstitial-cell-derived-matrix-vesicles
#5
Lin Cui, Nabil A Rashdan, Dongxing Zhu, Elspeth Milne, Paul Ajuh, Gillian Milne, Miep Helfrich, Kelvin Lim, Sai Prasad, Daniel Lerman, Alex Vesey, Marc Dweck, W S Jenkins, David Newby, Colin Farquharson, Vicky E Macrae
Patients with end-stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesised that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4 fold; P < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8 fold; P < 0...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28362018/il-37-suppresses-myd88-mediated-inflammatory-responses-in-human-aortic-valve-interstitial-cells
#6
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A Fullerton, Charles A Dinarello, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists...
March 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28356268/neurotrophin-3-up-regulates-proliferation-and-collagen-production-in-human-aortic-valve-interstitial-cells-a-potential-role-in-aortic-valve-sclerosis
#7
Qingzhou Yao, Rui Song, Lihua Ao, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and over-production of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves over-express growth factor neurotrophin 3 (NT3)...
March 29, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28332126/klotho-suppresses-high-phosphate-induced-osteogenic-responses-in-human-aortic-valve-interstitial-cells-through-inhibition-of-sox9
#8
Fei Li, Qingzhou Yao, Lihua Ao, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
Elevated level of blood phosphate (Pi) associated with chronic kidney disease (CKD) is a risk factor of aortic valve calcification. Aortic valve interstitial cells (AVICs) display osteogenic responses to high Pi although the underlying mechanism is incompletely understood. Sox9 is a pro-chondrogenic factor and may play a role in ectopic tissue calcification. Circulating and kidney levels of Klotho are reduced in patients with CKD. We hypothesized that Sox9 mediates high Pi-induced osteogenic responses in human AVICs and that Klotho inhibits the responses...
March 22, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28322869/scaffold-free-high-throughput-generation-of-quiescent-valvular-microtissues
#9
Annelies Roosens, Inès Puype, Ria Cornelissen
AIMS: The major challenge of working with valvular interstitial cells in vitro is the preservation or recovery of their native quiescent state. In this study, a biomimetic approach is used which aims to engineer small volume, high quality valve microtissues, having a potential in regenerative medicine and as a relevant 3D in vitro model to provide insights into valve (patho)biology. METHODS AND RESULTS: To form micro-aggregates, porcine valvular interstitial cells were seeded in agarose micro-wells and cultured in medium supplemented with 250μM Ascorbic Acid 2-phosphate for 22days...
March 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28319833/aortic-calcified-particles-modulate-valvular-endothelial-and-interstitial-cells
#10
Nicole C A van Engeland, Sergio Bertazzo, Padmini Sarathchandra, Ann McCormack, Carlijn V C Bouten, Magdi H Yacoub, Adrian H Chester, Najma Latif
BACKGROUND: Normal and calcified human valve cusps, coronary arteries, and aortae harbor spherical calcium phosphate microparticles of identical composition and crystallinity, and their role remains unknown. OBJECTIVE: The objective was to examine the direct effects of isolated calcified particles on human valvular cells. METHOD AND RESULTS: Calcified particles were isolated from healthy and diseased aortae, characterized, quantitated, and applied to valvular endothelial cells (VECs) and interstitial cells (VICs)...
March 3, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28314924/leptin-induces-osteoblast-differentiation-of-human-valvular-interstitial-cells-via-the-akt-and-erk-pathways
#11
Mickael Rosa, Camille Paris, Yoann Sottejeau, Delphine Corseaux, Emmanuel Robin, Madjid Tagzirt, Francis Juthier, Ramadan Jashari, Antoine Rauch, André Vincentelli, Bart Staels, Eric Van Belle, Sophie Susen, Annabelle Dupont
AIMS: Calcific aortic valve disease (CAVD) affects 2-6% of the population over 65 years, and age, gender, smoking, overweight, dyslipidemia, diabetes contribute to the development of this disease. CAVD results, in part, from the osteoblast differentiation of human valvular interstitial cells (VICs). This study aims to elucidate the effects of leptin on osteoblast phenotype of VICs and the signalling pathways involved. METHODS: Patients who underwent aortic valve replacement for CAVD (n = 43) were included in this study...
March 18, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28314761/hypoxia-mediated-regulation-of-the-secretory-properties-of-mitral-valve-interstitial-cells
#12
Kareem Salhiyyah, Padmini Sarathchandra, Najma Latif, Magdi H Yacoub, Adrian H Chester
The sophisticated function of the mitral valve depends to a large extent on the extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important pathway is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVIC) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulphated glycosaminoglycans (sGAG) in cultured porcine MVIC...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28292746/robust-generation-of-quiescent-porcine-valvular-interstitial-cell-cultures
#13
Ana M Porras, Nicole C A van Engeland, Evelyn Marchbanks, Ann McCormack, Carlijn V C Bouten, Magdi H Yacoub, Najma Latif, Kristyn S Masters
BACKGROUND: Valvular interstitial cells (VICs) in the healthy aortic valve leaflet exhibit a quiescent phenotype, with <5% of VICs exhibiting an activated phenotype. Yet, in vitro culture of VICs on tissue culture polystyrene surfaces in standard growth medium results in rapid transformation to an activated phenotype in >90% of cells. The inability to preserve a healthy VIC phenotype during in vitro studies has hampered the elucidation of mechanisms involved in calcific aortic valve disease...
March 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28283241/the-shift-of-macrophages-toward-m1-phenotype-promotes-aortic-valvular-calcification
#14
Geng Li, Weihua Qiao, Wenjing Zhang, Fei Li, Jiawei Shi, Nianguo Dong
OBJECTIVE: The purpose of the present study was to comprehensively compare the phenotype profile of infiltrated macrophages in human noncalcified and calcific aortic valves, and to determine whether the shift of macrophage polarization modulates valvular calcification in vitro. METHODS: Cell surface markers of macrophages and inflammatory cytokines expression in 90 cases of human noncalcified and calcific aortic valve leaflets were analyzed. The normal aortic valve interstitial cells were isolated and cultured in vitro...
February 9, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28260034/high-mobility-group-box-1-induces-calcification-of-aortic-valve-interstitial-cells-via-toll-like-receptor-4
#15
Wenjun Shen, Jianqing Zhou, Chaoyang Wang, Guangze Xu, Ying Wu, Zhaohui Hu
Chronic inflammation and the calcification of aortic valve interstitial cells (AVICs) are the primary etiologies of calcific aortic valve disease (CAVD). However, the underlying mechanism remains to be elucidated. The present study investigated the importance of high mobility group box 1 (HMGB1) via toll‑like receptor 4 (TLR4) for the regulation of inflammation and calcification in AVICs. It was determined that the expression levels of HMGB1 and TLR4 were increased in the calcific region of aortic valves with CAVD...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28256242/a-functionally-graded-material-model-for-the-transmural-stress-distribution-of-the-aortic-valve-leaflet
#16
Bruno V Rego, Michael S Sacks
Heterogeneities in structure and stress within heart valve leaflets are of significant concern to their functional physiology, as they affect how the tissue constituents remodel in response to pathological and non-pathological (e.g. exercise, pregnancy) alterations in cardiac function. Indeed, valve interstitial cells (VICs) are known to synthesize and degrade leaflet extracellular matrix (ECM) components in a manner specific to their local micromechanical environment. Quantifying local variations in ECM structure and stress is thus necessary to understand homeostatic valve maintenance as well as to develop predictive models of disease progression and post-surgical outcomes...
March 21, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28247311/elevated-serotonin-interacts-with-angiotensin-ii-to-result-in-altered-valve-interstitial-cell-contractility-and-remodeling
#17
Jessica Perez, Nancy Diaz, Ishita Tandon, Rachel Plate, Christopher Martindale, Kartik Balachandran
While the valvulopathic effects of serotonin (5HT) and angiotensin-II (Ang-II) individually are known, it was not clear how 5HT and Ang-II might interact, specifically in the context of the mechanobiological responses due to altered valve mechanics potentiated by these molecules. In this context, the hypothesis of this study was that increased serotonin levels would result in accelerated progression toward disease in the presence of angiotensin-II-induced hypertension. C57/BL6 J mice were divided into four groups and subcutaneously implanted with osmotic pumps containing: PBS (control), 5HT (2...
February 28, 2017: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/28220141/adhesive-peptide-sequences-regulate-valve-interstitial-cell-adhesion-phenotype-and-extracellular-matrix-deposition
#18
Yan Wu, K Jane Grande-Allen, Jennifer L West
Knowledge of how extracellular matrix (ECM) binding impacts valve interstitial cells (VICs) is critical not only to better understanding the etiology of valvular diseases but also to constructing living valve substitutes that can grow and remodel. Use of ECM-mimicking adhesive peptides with specific affinity to different receptors provides insights into adhesion-mediated cell signaling and downstream outcomes. Expression of adhesion receptors by VICs was assessed by flow cytometry and used to guide the choice of peptides studied...
December 2016: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/28208829/calcium-signaling-in-interstitial-cells-focus-on-telocytes
#19
REVIEW
Beatrice Mihaela Radu, Adela Banciu, Daniel Dumitru Banciu, Mihai Radu, Dragos Cretoiu, Sanda Maria Cretoiu
In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca(2+) oscillations, the inositol triphosphate (IP₃)/Ca(2+) signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28183649/biological-and-mechanical-evaluation-of-a-bio-hybrid-scaffold-for-autologous-valve-tissue-engineering
#20
S Jahnavi, U Saravanan, N Arthi, G S Bhuvaneshwar, T V Kumary, S Rajan, R S Verma
Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties...
April 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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