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https://www.readbyqxmd.com/read/29358327/low-level-overexpression-of-p53-promotes-warfarin-induced-calcification-of-porcine-aortic-valve-interstitial-cells-by-activating-slug-gene-transcription
#1
Li Gao, Yue Ji, Yan Lu, Ming Qiu, Yejiao Shen, Yaqing Wang, Xiangqing Kong, Yongfeng Shao, Yanhui Sheng, Wei Sun
The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), while the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic trans-differentiation and calcification of AVICs. Whether p53 participating in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification...
January 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348122/macrophage-transitions-in-heart-valve-development-and-myxomatous-valve-disease
#2
Alexia Hulin, Lindsey J Anstine, Andrew J Kim, Sarah J Potter, Tony DeFalco, Joy Lincoln, Katherine E Yutzey
OBJECTIVE: Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing and contribution of macrophages in normal valves and myxomatous valve disease are still unknown. The objective is to characterize leukocytes during postnatal heart valve maturation and identify macrophage subsets in myxomatous valve disease...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29338582/a-human-pericardium-biopolymeric-scaffold-for-autologous-heart-valve-tissue-engineering-cellular-and-extracellular-matrix-structure-and-biomechanical-properties-in-comparison-with-a-normal-aortic-heart-valve
#3
Frantisek Straka, David Schornik, Jaroslav Masin, Elena Filova, Tomas Mirejovsky, Zuzana Burdikova, Zdenek Svindrych, Hynek Chlup, Lukas Horny, Matej Daniel, Jiri Machac, Jelena Skibová, Jan Pirk, Lucie Bacakova
The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells (PICs), which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells (VICs) in NAV tissue. The extracellular matrix (ECM) of HP had a statistically significantly (p ≤ 0...
January 17, 2018: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/29315310/dysregulation-of-valvular-interstitial-cell-let-7c-mir-17-mir-20a-and-mir-30d-in-naturally-occurring-canine-myxomatous-mitral-valve-disease
#4
Vicky K Yang, Albert K Tai, Terry P Huh, Dawn M Meola, Christine M Juhr, Nicholas A Robinson, Andrew M Hoffman
Canine myxomatous mitral valve disease (MMVD) resembles the early stages of myxomatous pathology seen in human non-syndromic mitral valve prolapse, a common valvular heart disease in the adult human population. Canine MMVD is seen in older subjects, suggesting age-related epigenetic dysregulation leading to derangements in valvular cell populations and matrix synthesis or degradation. We hypothesized that valvular interstitial cells (VICs) undergo disease-relevant changes in miRNA expression. In primary VIC lines from diseased and control valves, miRNA expression was profiled using RT-qPCR and next generation sequencing...
2018: PloS One
https://www.readbyqxmd.com/read/29304157/conditional-deletion-of-rb1-in-the-tie2-lineage-leads-to-aortic-valve-regurgitation
#5
Marina Freytsis, Lauren Baugh, Zhiyi Liu, Irene Georgakoudi, Philip W Hinds, Lauren D Black, Gordon S Huggins
OBJECTIVE: Aortic valve disease is a complex process characterized by valve interstitial cell activation, disruption of the extracellular matrix culminating in valve mineralization occurring over many years. We explored the function of the retinoblastoma protein (pRb) in aortic valve disease, given its critical role in mesenchymal cell differentiation including bone development and mineralization. APPROACH AND RESULTS: We generated a mouse model of conditional pRb knockout (cKO) in the aortic valve regulated by Tie2-Cre-mediated excision of floxed RB1 alleles...
2018: PloS One
https://www.readbyqxmd.com/read/29291394/serotonin-receptor-2b-signaling-with-interstitial-cell-activation-and-leaflet-remodeling-in-degenerative-mitral-regurgitation
#6
Kathryn H Driesbaugh, Emanuela Branchetti, Juan B Grau, Samuel J Keeney, Kimberly Glass, Mark A Oyama, Nancy Rioux, Salma Ayoub, Michael S Sacks, John Quackenbush, Robert J Levy, Giovanni Ferrari
AIMS: Mitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed serotonin (5HT) dysregulation in cardiac valvulopathies; however, the impact of 5HT-mediated signaling on MVIC activation and leaflet remodeling in MVP have been investigated to a limited extent. Here we test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology...
December 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29286439/isolation-and-characterization-of-primary-rat-valve-interstitial-cells-a-new-model-to-study-aortic-valve-calcification
#7
Cui Lin, Dongxing Zhu, Greg Markby, Brendan M Corcoran, Colin Farquharson, Vicky E Macrae
Calcific aortic valve disease (CAVD) is characterized by the progressive thickening of the aortic valve leaflets. It is a condition frequently found in the elderly and end-stage renal disease (ESRD) patients, who commonly suffer from hyperphosphatemia and hypercalcemia. At present, there are no medication therapies that can stop its progression. The mechanisms that underlie this pathological process remain unclear. The aortic valve leaflet is composed of a thin layer of valve endothelial cells (VECs) on the outer surfaces of the aortic cusps, with valve interstitial cells (VICs) sandwiched between the VECs...
November 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29282325/creation-of-disease-inspired-biomaterial-environments-to-mimic-pathological-events-in-early-calcific-aortic-valve-disease
#8
Ana M Porras, Jennifer A Westlund, Austin D Evans, Kristyn S Masters
An insufficient understanding of calcific aortic valve disease (CAVD) pathogenesis remains a major obstacle in developing treatment strategies for this disease. The aim of the present study was to create engineered environments that mimic the earliest known features of CAVD and apply this in vitro platform to decipher relationships relevant to early valve lesion pathobiology. Glycosaminoglycan (GAG) enrichment is a dominant hallmark of early CAVD, but culture of valvular interstitial cells (VICs) in biomaterial environments containing pathological amounts of hyaluronic acid (HA) or chondroitin sulfate (CS) did not directly increase indicators of disease progression such as VIC activation or inflammatory cytokine production...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29273600/deficiency-of-natriuretic-peptide-receptor-2-promotes-bicuspid-aortic-valves-aortic-valve-disease-left-ventricular-dysfunction-and-ascending-aortic-dilatations-in-mice
#9
Mark C Blaser, Kuiru Wei, Rachel L Adams, Yu-Qing Zhou, Laura-Lee Caruso, Zahra Mirzaei, Alan Lam, Richard K Tam, Hangjun Zhang, Scott P Heximer, Mark Henkelman, Craig A Simmons
Rationale: Aortic valve disease is a cell-mediated process without effective pharmacotherapy. C-type natriuretic peptide (CNP) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells (VICs), and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo. Objective: To determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease. Methods and Results: In cultured porcine VICs, CNP inhibited pathological differentiation via the guanylate cyclase natriuretic peptide receptor 2 (NPR2) and not the G-protein-coupled clearance receptor NPR3...
December 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/29244962/expression-of-the-frizzled-receptors-and-their-co-receptors-in-calcified-human-aortic-valves
#10
Ateeque Siddique, Bin Yu, Kashif Khan, Ryan Buyting, Hamood Al-Kindi, Hossny Alaws, Eric Rhéaume, Jean-Claude Tardif, Renzo Cecere, Adel Schwertani
The cellular mechanisms that induce calcific aortic stenosis are yet to be unravelled. Wnt signaling is increasingly being considered as a major player in the disease process. However, the presence of Wnt Frizzled receptors (Fzd) and co-receptors LRP5 and 6 in normal and diseased human aortic valves remains to be elucidated. Immunohistochemistry and qPCR were used to determine Fzd receptor expression in normal and calcified human aortic valve tissue, as well as human aortic valve interstitial cells (HAVICs) isolated from calcified and normal human aortic valves...
December 15, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29227539/mir-29b-promotes-human-aortic-valve-interstitial-cell-calcification-via-inhibiting-tgf-%C3%AE-3-through-activation-of-wnt3-%C3%AE-catenin-smad3-signaling
#11
Ming Fang, Cheng-Guang Wang, Changzhu Zheng, Jun Luo, Shiqiang Hou, Kangyong Liu, Xinming Li
Herein, we hypothesized that pro-osteogenic MicroRNAs (miRs) could play functional roles in the calcification of the aortic valve and aimed to explore the functional role of miR-29b in the osteoblastic differentiation of human aortic valve interstitial cells (hAVICs) and the underlying molecular mechanism. Osteoblastic differentiation of hAVICs isolated from human calcific aortic valve leaflets obtained intraoperatively was induced with an osteogenic medium. Alizarin red S staining was used to evaluate calcium deposition...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29207136/exploiting-novel-valve-interstitial-cell-lines-to-study-calcific-aortic-valve-disease
#12
Hiu-Gwen Tsang, Lin Cui, Colin Farquharson, Brendan M Corcoran, Kim M Summers, Vicky E Macrae
Calcific aortic valve disease (CAVD) involves progressive valve leaflet thickening and severe calcification, impairing leaflet motion. The in vitro calcification of primary rat, human, porcine and bovine aortic valve interstitial cells (VICs) is commonly employed to investigate CAVD mechanisms. However, to date, no published studies have utilised cell lines to investigate this process. The present study has therefore generated and evaluated the calcification potential of immortalized cell lines derived from sheep and rat VICs...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29191508/in-vivo-performance-of-freeze-dried-decellularized-pulmonary-heart-valve-allo-and-xenografts-orthotopically-implanted-into-juvenile-sheep
#13
Tobias Goecke, Karolina Theodoridis, Igor Tudorache, Anatol Ciubotaru, Serghei Cebotari, Robert Ramm, Klaus Höffler, Samir Sarikouch, Andrés Vásquez-Rivera, Axel Haverich, Willem F Wolkers, Andres Hilfiker
The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution...
November 27, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29176317/downregulated-microrna-195-in-the-bicuspid-aortic-valve-promotes-calcification-of-valve-interstitial-cells-via-targeting-smad7
#14
Junjie Du, Rui Zheng, Feng Xiao, Shuai Zhang, Keshuai He, Junjie Zhang, Yongfeng Shao
BACKGROUND/AIMS: Aortic stenosis caused by leaflet calcification in the bicuspid aortic valve (BAV) is more accelerative than that in the tricuspid aortic valve (TAV). MicroRNA-195 (miR-195) is downregulated more in stenotic than in insufficient BAVs, but its expression in BAVs compared with TAVs is unclear. We aimed to investigate the roles of miR-195 and its calcification-related target SMAD7 in stenotic BAVs compared with those in TAVs. METHODS: Twenty-one stenotic BAV and 29 TAV samples were collected from surgical patients and examined for the expression of miR-195 and SMAD7 by RT-PCR...
November 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29158034/different-notch-signaling-in-cells-from-calcified-bicuspid-and-tricuspid-aortic-valves
#15
A Kostina, A Shishkova, E Ignatieva, O Irtyuga, M Bogdanova, K Levchuk, A Golovkin, E Zhiduleva, V Uspenskiy, O Moiseeva, G Faggian, J Vaage, A Kostareva, A Rutkovskiy, A Malashicheva
AIMS: Calcific aortic valve disease is the most common heart valve disease in the Western world. Bicuspid and tricuspid aortic valve calcifications are traditionally considered together although the dynamics of the disease progression is different between the two groups of patients. Notch signaling is critical for bicuspid valve development and NOTCH1 mutations are associated with bicuspid valve and calcification. We hypothesized that Notch-dependent mechanisms of valve mineralization might be different in the two groups...
November 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29148548/acrylate-based-materials-for-heart-valve-scaffold-engineering
#16
Rosaria Santoro, Seshasailam Venkateswaran, Francesco Amadeo, Rong Zhang, Maura Brioschi, Anthony Callanan, Marco Agrifoglio, Cristina Banfi, Mark Bradley, Maurizio Pesce
Calcific aortic valve disease (CAVD) is the most frequent cardiac valve pathology. Its standard treatment consists of surgical replacement either with mechanical (metal made) or biological (animal tissue made) valve prostheses, both of which have glaring deficiencies. In the search for novel materials to manufacture artificial valve tissue, we have conducted a high-throughput screening with subsequent up-scaling to identify non-degradable polymer substrates that promote valve interstitial cells (VICs) adherence/growth and, at the same time, prevent their evolution toward a pro-calcific phenotype...
November 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29131080/complete-static-repopulation-of-decellularized-porcine-tissues-for-heart-valve-engineering-an-in-vitro-study
#17
Annelies Roosens, Mahtab Asadian, Nathalie De Geyter, Pamela Somers, Ria Cornelissen
To date, a completely in vitro repopulated tissue-engineered heart valve has not been developed. This study focused on sequentially seeding 2 cell populations onto porcine decellularized heart valve leaflets (HVL) and pericardia (PER) to obtain fully repopulated tissues. For repopulation of the interstitium, porcine valvular interstitial cells (VIC) and bone marrow-derived mesenchymal stem cells (BM-MSC) or adipose tissue-derived stem cells (ADSC) were used. In parallel, the culture medium was supplemented with ascorbic acid 2-phosphate (AA) and its effect on recolonization was investigated...
November 8, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/29054843/contribution-of-extra-cardiac-cells-in-murine-heart-valves-is-age-dependent
#18
Lindsey J Anstine, Tori E Horne, Edwin M Horwitz, Joy Lincoln
BACKGROUND: Heart valves are dynamic structures that open and close over 100 000 times a day to maintain unidirectional blood flow during the cardiac cycle. Function is largely achieved by highly organized layers of extracellular matrix that provide the necessary biomechanical properties. Homeostasis of valve extracellular matrix is mediated by valve endothelial and interstitial cell populations, and although the embryonic origins of these cells are known, it is not clear how they are maintained after birth...
October 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29046338/regulation-of-valve-interstitial-cell-homeostasis-by-mechanical-deformation-implications-for-heart-valve-disease-and-surgical-repair
#19
Salma Ayoub, Chung-Hao Lee, Kathryn H Driesbaugh, Wanda Anselmo, Connor T Hughes, Giovanni Ferrari, Robert C Gorman, Joseph H Gorman, Michael S Sacks
Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level in vivo state and in vitro-based mechanobiology studies has yet to be made. We thus developed an integrated experimental-computational approach to elucidate MV tissue and interstitial cell responses to varying tissue strain levels...
October 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29026447/epigenome-alterations-in-aortic-valve-stenosis-and-its-related-left-ventricular-hypertrophy
#20
REVIEW
Igor Gošev, Martina Zeljko, Željko Đurić, Ivana Nikolić, Milorad Gošev, Sanja Ivčević, Dino Bešić, Zoran Legčević, Frane Paić
Aortic valve stenosis is the most common cardiac valve disease, and with current trends in the population demographics, its prevalence is likely to rise, thus posing a major health and economic burden facing the worldwide societies. Over the past decade, it has become more than clear that our traditional genetic views do not sufficiently explain the well-known link between AS, proatherogenic risk factors, flow-induced mechanical forces, and disease-prone environmental influences. Recent breakthroughs in the field of epigenetics offer us a new perspective on gene regulation, which has broadened our perspective on etiology of aortic stenosis and other aortic valve diseases...
2017: Clinical Epigenetics
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