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https://www.readbyqxmd.com/read/28821833/microrna-449c-5p-inhibits-osteogenic-differentiation-of-human-vics-through-smad4-mediated-pathway
#1
Rongjian Xu, Min Zhao, Yun Yang, Zhuo Huang, Chunying Shi, Xianglin Hou, Yannan Zhao, Bing Chen, Zhifeng Xiao, Jianzhou Liu, Qi Miao, Jianwu Dai
Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732089/cx47-fine-tunes-the-handling-of-serum-lipids-but-is-dispensable-for-lymphatic-vascular-function
#2
Merlijn J Meens, Issa Kutkut, Viviane Rochemont, Juan Dubrot, Fouad R Kaladji, Amélie Sabine, Oliver Lyons, Stefanie Hendrikx, Jeremiah Bernier-Latmani, Friedemann Kiefer, Alberto Smith, Stéphanie Hugues, Tatiana V Petrova, Brenda R Kwak
Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency...
2017: PloS One
https://www.readbyqxmd.com/read/28620766/phenotype-transformation-of-aortic-valve-interstitial-cells-due-to-applied-shear-stresses-within-a-microfluidic-chip
#3
Xinmei Wang, Joohyung Lee, Mir Ali, Jungkyu Kim, Carla M R Lacerda
Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses...
June 15, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#4
Maximillian A Rogers, Natalia Maldonado, Joshua D Hutcheson, Claudia Goettsch, Shinji Goto, Iwao Yamada, Tyler Faits, Hiromi Sesaki, Masanori Aikawa, Elena Aikawa
RATIONALE: Mitochondrial changes occur during cell differentiation and cardiovascular disease. DRP1 (dynamin-related protein 1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. OBJECTIVE: To examine the effects of osteogenic promoting conditions on DRP1 and whether DRP1 inhibition alters the development of cardiovascular calcification...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28601321/lysophosphatidylcholine-activates-the-akt-pathway-to-upregulate-extracellular-matrix-protein-production-in-human-aortic-valve-cells
#5
Hui Cheng, Qingzhou Yao, Rui Song, Yufeng Zhai, Wei Wang, David A Fullerton, Xianzhong Meng
BACKGROUND: Overproduction of extracellular matrix (ECM) protein by aortic valve interstitial cells (AVICs) plays an important role in valvular sclerosis (thickening) associated with the early pathobiology of aortic stenosis. Accumulation of oxidized low-density lipoprotein (oxLDL) is observed in sclerotic aortic valve and may have a mechanistic role in valvular disease progression. Lysophosphatidylcholine (LysoPC) is a component of oxLDL and has multiple biological activities. This study was to test the hypothesis that oxLDL and LysoPC upregulate ECM protein production in human AVICs...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28546218/adamts5-deficiency-in-calcified-aortic-valves-is-associated-with-elevated-pro-osteogenic-activity-in-valvular-interstitial-cells
#6
Fei Li, Rui Song, Lihua Ao, T Brett Reece, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
OBJECTIVE: Extracellular matrix proteinases are implicated in the pathogenesis of calcific aortic valve disease. The ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) enzyme is secreted, matrix-associated metalloendopeptidase, capable of degrading extracellular matrix proteins, particularly matrilin 2. We sought to determine the role of the ADAMTS5/matrilin 2 axis in mediating the phenotype transition of valvular interstitial cells (VICs) associated with calcific aortic valve disease...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28536843/human-interstitial-cellular-model-in-therapeutics-of-heart-valve-calcification
#7
REVIEW
Caimei He, Hai Tang, Zijian Mei, Nichujie Li, Zhi Zeng, Kwame Oteng Darko, Yulong Yin, Chien-An Andy Hu, Xiaoping Yang
Calcific aortic valve disease is a common, severe heart condition that is currently with no proven, effective drug treatment and requires a surgical valve replacement or an entire heart explanation. Thus, developing novel, targeted therapeutic approaches becomes a major goal for cardiovascular disease research. To achieve this goal, isolated heart valve interstitial cells could be an advanced model to explore molecular mechanisms and measure drug efficacy. Based on this progress, molecular mechanisms that harbor components of  inflammation and fibrosis coupled with proteins, for example, BMP-2, TLRs, RANKL, Osteoprotegerin, have been proposed...
May 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28522163/lncrna-malat1-sponges-mir-204-to-promote-osteoblast-differentiation-of-human-aortic-valve-interstitial-cells-through-up-regulating-smad4
#8
Xiaoxiong Xiao, Tingwen Zhou, Shichao Guo, Chao Guo, Qiao Zhang, Nianguo Dong, Yongjun Wang
BACKGROUND: Emerging evidences have indicated that long non-coding RNAs (lncRNAs) play vital roles in cardiovascular physiology and pathology. The lncRNA MALAT1, a highly abundant and conserved imprinted gene, has been implicated in many cardiovascular diseases. However, the function of MALAT1 in calcific aortic valve disease (CAVD) remains unknown. This study sought to document the function and underlying mechanism of MALAT1 in regulating CAVD. METHODS: Protein level was determined by immunoblotting and immunofluorescence staining...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28516795/a-comprehensive-guide-to-telocytes-and-their-great-potential-in-cardiovascular-system
#9
REVIEW
I Kucybala, P Janas, S Ciuk, W Cholopiak, W Klimek-Piotrowska, M K Holda
Telocytes, a recently discovered type of interstitial cells, have a very distinctive morphology - the small cell body with long extensions, named telopodes. In our review, apart from introducing general aspects of telocytes, we focus on properties, functions and future potential of those cells in cardiovascular system. However, physiological functions of telocytes in cardiovascular system are still regarded as quite enigmatic. Previous studies claim that they play a role in organogenesis and regeneration, bioelectrical signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis and regulation of blood flow...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28488393/in-vitro-analysis-of-early-calcification-in-aortic-valvular-interstitial-cells-using-laser-induced-breakdown-spectroscopy-libs
#10
Seyyed Ali Davari, Shirin Masjedi, Zannatul Ferdous, Dibyendu Mukherjee
Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages...
May 9, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28484097/fabrication-of-a-matrigel-collagen-semi-interpenetrating-scaffold-for-use-in-dynamic-valve-interstitial-cell-culture
#11
Ngoc Lam, Hanh Lam, Nasya Sturdivant, Kartik Balachandran
The study of heart valve homeostatic and disease mechanisms are often limited by the challenges in simulating the in vivo milieu, where valve cells are surrounded by the extracellular matrix in a three dimensional environment and experience multiple dynamic mechanical forces. Type I collagen is typically the most common three dimensional matrix used to culture valve cells in vitro. Unfortunately, this material has poor mechanical behavior due to an inherent propensity to compact significantly, unlike native valve leaflets...
May 9, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28472283/oxldl-derived-lysophosphatidic-acid-promotes-the-progression-of-aortic-valve-stenosis-through-a-lpar1-rhoa-nf-%C3%AE%C2%BAb-pathway
#12
Mohamed Jalloul Nsaibia, Marie-Chloé Boulanger, Rihab Bouchareb, Ghada Mkannez, Khai Le Quang, Fayez Hadji, Deborah Argaud, Abdellaziz Dahou, Yohan Bossé, Marlys L Koschinsky, Philippe Pibarot, Benoit J Arsenault, André Marette, Patrick Mathieu
AIMS: Oxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least 6 different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28455837/valve-interstitial-cell-culture-production-of-mature-type-i-collagen-and-precise-detection
#13
Jana Liskova, Daniel Hadraba, Elena Filova, Miroslav Konarik, Jan Pirk, Karel Jelen, Lucie Bacakova
Collagen often acts as an extracellular and intracellular marker for in vitro experiments, and its quality defines tissue constructs. To validate collagen detection techniques, cardiac valve interstitial cells were isolated from pigs and cultured under two different conditions; with and without ascorbic acid. The culture with ascorbic acid reached higher cell growth and collagen deposition, although the expression levels of collagen gene stayed similar to the culture without ascorbic acid. The fluorescent microscopy was positive for collagen fibers in both the cultures...
April 28, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28453968/association-of-altered-collagen-content-and-lysyl-oxidase-expression-in-degenerative-mitral-valve-disease
#14
K-Raman Purushothaman, Meerarani Purushothaman, Irene C Turnbull, David H Adams, Anelechi Anyanwu, Prakash Krishnan, Annapoorna Kini, Samin K Sharma, William N O'Connor, Pedro R Moreno
BACKGROUND: Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity. METHODS: Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls...
July 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28438736/altered-microrna-expression-is-responsible-for-the-pro-osteogenic-phenotype-of-interstitial-cells-in-calcified-human-aortic-valves
#15
Rui Song, David A Fullerton, Lihua Ao, Ke-Seng Zhao, T Brett Reece, Joseph C Cleveland, Xianzhong Meng
BACKGROUND: The transition of aortic valve interstitial cells (AVICs) to myofibroblastic and osteoblast-like phenotypes plays a critical role in calcific aortic valve disease progression. Several microRNAs (miRs) are implicated in stem cell differentiation into osteoblast. We hypothesized that an epigenetic mechanism regulates valvular pro-osteogenic activity. This study examined miR profile in AVICs of calcified valves and identified miRs responsible for AVIC phenotypic transition. METHODS AND RESULTS: AVICs were isolated from normal and diseased valves...
April 24, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28429161/on-the-in-vivo-function-of-the-mitral-heart-valve-leaflet-insights-into-tissue-interstitial-cell-biomechanical-coupling
#16
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
#17
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
#18
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...
July 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
#19
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 β1 (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...
May 26, 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
#20
Lin Cui, Nabil A Rashdan, Dongxing Zhu, Elspeth M Milne, Paul Ajuh, Gillian Milne, Miep H Helfrich, Kelvin Lim, Sai Prasad, Daniel A Lerman, Alex T Vesey, Marc R Dweck, William S Jenkins, David E 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 hypothesized 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
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