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https://www.readbyqxmd.com/read/28332126/klotho-suppresses-high-phosphate-induced-osteogenic-responses-in-human-aortic-valve-interstitial-cells-through-inhibition-of-sox9
#1
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
#2
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 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28319833/aortic-calcified-particles-modulate-valvular-endothelial-and-interstitial-cells
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
February 8, 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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#14
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28157139/genetic-basis-of-aortic-valvular-disease
#15
Sara N Koenig, Joy Lincoln, Vidu Garg
PURPOSE OF REVIEW: Aortic valve disease is relatively common and encompasses both congenital and acquired forms. Bicuspid aortic valve (BAV) is the most common type of cardiac malformation and predisposes to the development of calcific aortic valve disease (CAVD). Since the description of the link between NOTCH1, BAV and CAVD approximately a decade ago, there have been significant advances in the genetic and molecular understanding of these diseases. RECENT FINDINGS: Recent work has defined the congenital cardiac phenotypes linked to mutations in NOTCH1, and in addition, novel etiologic genes for BAV have been discovered using new genetic technologies in humans...
February 2, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28137840/interleukin-37-suppresses-the-osteogenic-responses-of-human-aortic-valve-interstitial-cells-in-vitro-and-alleviates-valve-lesions-in-mice
#16
Qingchun Zeng, Rui Song, David A Fullerton, Lihua Ao, Yufeng Zhai, Suzhao Li, Dov B Ballak, Joseph C Cleveland, T Brett Reece, Timothy A McKinsey, Dingli Xu, Charles A Dinarello, Xianzhong Meng
Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28112549/survival-related-autophagic-activity-versus-procalcific-death-in-cultured-aortic-valve-interstitial-cells-treated-with-critical-normophosphatemic-like-phosphate-concentrations
#17
Antonella Bonetti, Alberto Della Mora, Magali Contin, Giorgia Gregoraci, Franco Tubaro, Maurizio Marchini, Fulvia Ortolani
Valve dystrophic calcification is a common disorder affecting normophosphatemic subjects. Here, cultured aortic valve interstitial cells (AVICs) were treated 3 to 28 days with phosphate (Pi) concentrations spanning the normal range in humans (0.8, 1.3, and 2.0 mM) alone or supplemented with proinflammatory stimuli to assess possible priming of dystrophic-like calcification. Compared with controls, spectrophotometric analyses revealed marked increases in calcium amounts and alkaline phosphatase activity for 2...
March 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28111052/activated-p300-acetyltransferase-activity-modulates-aortic-valvular-calcification-with-osteogenic-transdifferentiation-and-downregulation-of-klotho
#18
Shao-Jung Li, Yu-Hsun Kao, Cheng-Chih Chung, Wei-Yu Chen, Wan-Li Cheng, Yi-Jen Chen
BACKGROUND: The calcific aortic valve (AV) disease is a common disease with the unclear mechanism, and optimal pharmacological treatment remains unavailable. Epigenetic modulation by histone acetyltransferase (HAT) plays a critical role in osteogenic transdifferentiation and atherosclerosis. The purposes of this study were to investigate whether HAT contributes to the pathophysiology of AV calcification and assess the therapeutic potential of HAT inhibition. METHODS: Porcine valvular interstitial cells (VICs) were treated with osteogenic medium (10ng/mL of tumor necrosis factor-α and 4mmol/L of high phosphate) for 7days...
January 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28110071/living-nano-micro-fibrous-woven-fabric-hydrogel-composite-scaffolds-for-heart-valve-engineering
#19
Shaohua Wu, Bin Duan, Xiaohong Qin, Jonathan T Butcher
Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation...
January 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28109865/a-survey-of-membrane-receptor-regulation-in-valvular-interstitial-cells-cultured-under-mechanical-stresses
#20
Mir S Ali, Xinmei Wang, Carla M R Lacerda
Degenerative valvular diseases have been linked to the action of abnormal forces on valve tissues during each cardiac cycle. It is now accepted that the degenerative behavior of valvular cells can be induced mechanically in vitro. This approach of in vitro modeling of valvular cells in culture constitutes a powerful tool to study, characterize, and develop predictors of heart valve degeneration in vivo. Using such in vitro systems, we expect to determine the exact signaling mechanisms that trigger and mediate propagation of degenerative signals...
February 15, 2017: Experimental Cell Research
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