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https://www.readbyqxmd.com/read/27866029/understanding-the-structural-features-of-symptomatic-calcific-aortic-valve-stenosis-a-broad-spectrum-clinico-pathologic-study-in-236-consecutive-surgical-cases
#1
Daniela Galli, Roberta Manuguerra, Rodolfo Monaco, Laura Manotti, Matteo Goldoni, Gabriella Becchi, Cecilia Carubbi, Giulia Vignali, Nicola Cucurachi, Tiziano Gherli, Francesco Nicolini, Roberto Lorusso, Marco Vitale, Domenico Corradi
BACKGROUND: With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS. METHODS: We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27856308/dysregulation-of-hyaluronan-homeostasis-during-aortic-valve-disease
#2
Varun K Krishnamurthy, Andrew J Stout, Matthew C Sapp, Brittany Matuska, Mark E Lauer, K Jane Grande-Allen
Aortic valve disease (AVD) is one of the leading causes of cardiovascular mortality. Abnormal expression of hyaluronan (HA) and its synthesizing/degrading enzymes have been observed during latent AVD however, the mechanism of impaired hyaluronan homeostasis prior to and after the onset of AVD remains unexplored. Transforming growth factor beta (TGFβ) pathway defects and biomechanical dysfunction are hallmarks of AVD, however their association with altered hyaluronan regulation is understudied. Expression of HA homeostatic markers was evaluated in diseased human aortic valves and TGFβ1-cultured porcine aortic valve tissues using histology, immunohistochemistry and Western blotting...
November 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27815266/role-for-galectin-3-in-calcific-aortic-valve-stenosis
#3
J Rafael Sádaba, Ernesto Martínez-Martínez, Vanessa Arrieta, Virginia Álvarez, Amaya Fernández-Celis, Jaime Ibarrola, Amaia Melero, Patrick Rossignol, Victoria Cachofeiro, Natalia López-Andrés
BACKGROUND: Aortic stenosis (AS) is a chronic inflammatory disease, and calcification plays an important role in the progression of the disease. Galectin-3 (Gal-3) is a proinflammatory molecule involved in vascular osteogenesis in atherosclerosis. Therefore, we hypothesized that Gal-3 could mediate valve calcification in AS. METHODS AND RESULTS: Blood samples and aortic valves (AVs) from 77 patients undergoing AV replacement were analyzed. As controls, noncalcified human AVs were obtained at autopsy (n=11)...
November 4, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27789555/altered-dna-methylation-of-long-non-coding-rna-h19-in-calcific-aortic-valve-disease-promotes-mineralization-by-silencing-notch1
#4
Fayez Hadji, Marie-Chloé Boulanger, Simon-Pierre Guay, Nathalie Gaudreault, Soumiya Amellah, Ghada Mkannez, Rihab Bouchareb, Joël Tremblay-Marchand, Mohamed Jalloul Nsaibia, Sandra Guauque-Olarte, Philippe Pibarot, Luigi Bouchard, Yohan Bossé, Patrick Mathieu
BACKGROUND: -Calcific aortic valve disease (CAVD) is characterized by an abnormal mineralization of the aortic valve. Osteogenic activity in the aortic valve is under the control of NOTCH1, which regulates the expression of key pro-osteogenic genes such as RUNX2 and BMP2 Long non-coding RNAs (lncRNAs) may reprogram cells by altering the gene expression pattern. METHODS: -Multidimensional genomic profiling was performed in human aortic valves to document the expression of lncRNAs and the DNA methylation pattern in CAVD...
October 27, 2016: Circulation
https://www.readbyqxmd.com/read/27789554/lnc-ing-notch1-to-idiopathic-calcific-aortic-valve-disease
#5
W David Merryman, Cynthia R Clark
Calcific aortic valve disease (CAVD) is an age-related disorder that causes significant cardiovascular morbidity and mortality, and is directly responsible for ~15,000 patient deaths per year in the USA. Currently, the molecular mechanism by which CAVD initiates is unknown, making discovery of a non-surgical strategy challenging (reviewed in (1)). Garg et al. made a seminal discovery in 2005 when they showed NOTCH1 mutations led to heritable CAVD.(2) Since then, the heart valve research community has sought a causal mechanism that could connect NOTCH1 dysfunction to idiopathic CAVD...
October 27, 2016: Circulation
https://www.readbyqxmd.com/read/27783858/heart-valve-biomechanics-and-underlying-mechanobiology
#6
Salma Ayoub, Giovanni Ferrari, Robert C Gorman, Joseph H Gorman, Frederick J Schoen, Michael S Sacks
Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27761653/sex-related-differences-in-matrix-remodeling-and-early-osteogenic-markers-in-aortic-valvular-interstitial-cells
#7
Shirin Masjedi, Ying Lei, Jenny Patel, Zannatul Ferdous
Calcific aortic valve disease (CAVD) is a major cardiovascular disorder in the developed countries. Male is a known risk factor in this disease; unfortunately, how sex contributes to CAVD is mostly unknown. The objective of this study is to determine whether valvular interstitial cells (VICs) isolated from male versus female aortic valves demonstrate difference in osteogenic differentiation and/or extracellular matrix (ECM) remodeling. VICs were isolated from male and female rat or porcine aortic valves and cultured in osteogenic media for 10, 15 and 20 days...
October 19, 2016: Heart and Vessels
https://www.readbyqxmd.com/read/27750208/cd45-expression-in-mitral-valve-endothelial-cells-after-myocardial-infarction
#8
Joyce Bischoff, Guillem Casanovas, Jill Wylie-Sears, Dae-Hee Kim, Philipp Bartko, J Guerrero, Jacob Dal-Bianco, Jonathan Beaudoin, Michael Garcia, Suzanne Sullivan, Margo Seybolt, Brittan Morris, Joshua Keegan, Whitney Irvin, Elena Aikawa, Robert Levine
RATIONALE: Ischemic mitral regurgitation (IMR), a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial, but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to IMR. OBJECTIVE: Endothelial, interstitial and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post-MI, was analyzed in vitro...
October 6, 2016: Circulation Research
https://www.readbyqxmd.com/read/27713997/valve-interstitial-cell-contractile-strength-and-metabolic-state-are-dependent-on-its-shape
#9
Ngoc Thien Lam, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram, Kartik Balachandran
The role of valvular interstitial cell (VIC) architecture in regulating cardiac valve function and pathology is not well understood. VICs are known to be more elongated in a hypertensive environment compared to those in a normotensive environment. We have previously reported that valve tissues cultured under hypertensive conditions are prone to acute pathological alterations in cell phenotype and contractility. We therefore aimed to rigorously study the relationship between VIC shape, contractile output and other functional indicators of VIC pathology...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/27641300/performance-of-allogeneic-bioengineered-replacement-pulmonary-valves-in-rapidly-growing-young-lambs
#10
Rachael W Quinn, Arthur A Bert, Gabriel L Converse, Eric E Buse, Stephen L Hilbert, William B Drake, Richard A Hopkins
BACKGROUND: Cardiac allometric organ growth after pediatric valve replacement can lead to patient-prosthesis size mismatch and valve re-replacement, which could be mitigated with allogeneic decellularized pulmonary valves treated with collagen conditioning solutions to enhance biological and mechanical performance, termed "bioengineered valves." In this study, we evaluated functional, dimensional, and biological responses of these bioengineered valves compared with traditional cryopreserved valves implanted in lambs during rapid somatic growth...
October 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27567567/valve-interstitial-cell-shape-modulates-cell-contractility-independent-of-cell-phenotype
#11
Ishita Tandon, Atefeh Razavi, Prashanth Ravishankar, Addison Walker, Nasya M Sturdivant, Ngoc Thien Lam, Jeffrey C Wolchok, Kartik Balachandran
Valve interstitial cells are dispersed throughout the heart valve and play an important role in maintaining its integrity, function, and phenotype. While prior studies have detailed the role of external mechanical and biological factors in the function of the interstitial cell, the role of cell shape in regulating contractile function, in the context of normal and diseased phenotypes, is not well understood. Thus, the aim of this study was to elucidate the link between cell shape, phenotype, and acute functional contractile output...
October 3, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27553639/spatial-expression-of-components-of-a-calcitonin-receptor-like-receptor-crl-signalling-system-crl-calcitonin-gene-related-peptide-adrenomedullin-adrenomedullin-2-intermedin-in-mouse-and-human-heart-valves
#12
Uwe Pfeil, Subhashini Bharathala, Ghulam Murtaza, Petra Mermer, Tamara Papadakis, Andreas Boening, Wolfgang Kummer
Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling...
August 23, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27497058/valve-interstitial-cell-tensional-homeostasis-directs-calcification-and-extracellular-matrix-remodeling-processes-via-rhoa-signaling
#13
Emily J Farrar, Varsha Pramil, Jennifer M Richards, Christopher Z Mosher, Jonathan T Butcher
AIMS: Valve interstitial cells are active and aggressive players in aortic valve calcification, but their dynamic mediation of mechanically-induced calcific remodeling is not well understood. The goal of this study was to elucidate the feedback loop between valve interstitial cell and calcification mechanics using a novel three-dimensional culture system that allows investigation of the active interplay between cells, disease, and the mechanical valve environment. METHODS & RESULTS: We designed and characterized a novel bioreactor system for quantifying aortic valve interstitial cell contractility in 3-D hydrogels in control and osteogenic conditions over 14 days...
October 2016: Biomaterials
https://www.readbyqxmd.com/read/27496484/brca1-reflects-myocardial-adverse-remodeling-in-idiopathic-dilated-cardiomyopathy
#14
J K Nozynski, D Konecka-Mrowka, M Zakliczynski, E Zembala-Nozynska, D Lange, M Zembala
BACKGROUND: The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS: The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27468412/denosumab-could-be-a-potential-inhibitor-of-valvular-interstitial-cells-calcification-in-vitro
#15
Daniel Alejandro Lerman, Sai Prasad, Nasri Alotti
OBJECTIVE: Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-β ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. We aimed to elucidate the effect of Denosumab in the process of spontaneous and induced calcification in an in vitro porcine valvular interstitial cells (VICs) model. MATERIALS AND METHODS: VICs were extracted from fresh porcine hearts by serial collagenase digestion...
January 3, 2016: International Journal of Cardiovascular Research
https://www.readbyqxmd.com/read/27450324/normal-human-mitral-valve-proteome-a-preliminary-investigation-by-gel-based-and-gel-free-proteomic-approaches
#16
Maura Brioschi, Roberta Baetta, Stefania Ghilardi, Erica Gianazza, Anna Guarino, Alessandro Parolari, Gianluca Polvani, Elena Tremoli, Cristina Banfi
The mitral valve is a highly complex structure which regulates blood flow from the left atrium to the left ventricle (LV) avoiding a significant forward gradient during diastole or regurgitation during systole. The integrity of the mitral valve is also essential for the maintenance of normal LV size, geometry, and function. Significant advances in the comprehension of the biological, functional, and mechanical behavior of the mitral valve have recently been made. However, current knowledge of protein components in the normal human mitral valve is still limited and complicated by the low cellularity of this tissue and the presence of high abundant proteins from the extracellular matrix...
October 2016: Electrophoresis
https://www.readbyqxmd.com/read/27441481/interleukin-18-promotes-myofibroblast-activation-of-valvular-interstitial-cells
#17
Jingxin Zhou, Jinfu Zhu, Li Jiang, Busheng Zhang, Dan Zhu, Yanhu Wu
BACKGROUND: Calcific aortic valve disease is the main heart valve disease in the elderly. Valvular interstitial cells (VICs) play an important role in the process of valve calcification. Interleukin 18 (IL-18) is expressed in stenosis aortic valves and is positively related with the clinical severity of aortic stenosis. However, the role of IL-18 in aortic valve calcification remains unclear. This study examined whether IL-18 promotes myofibroblast and/or osteoblast transdifferention of VICs...
October 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27420053/micrornas-in-valvular-heart-diseases-potential-role-as-markers-and-actors-of-valvular-and-cardiac-remodeling
#18
REVIEW
Cécile Oury, Laurence Servais, Nassim Bouznad, Alexandre Hego, Alain Nchimi, Patrizio Lancellotti
miRNAs are a class of over 5000 noncoding RNAs that regulate more than half of the protein-encoding genes by provoking their degradation or preventing their translation. miRNAs are key regulators of complex biological processes underlying several cardiovascular disorders, including left ventricular hypertrophy, ischemic heart disease, heart failure, hypertension and arrhythmias. Moreover, circulating miRNAs herald promise as biomarkers in acute myocardial infarction and heart failure. In this context, this review gives an overview of studies that suggest that miRNAs could also play a role in valvular heart diseases...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27395056/the-role-of-high-mobility-group-box-1-protein-in-interleukin-18-induced-myofibroblastic-transition-of-valvular-interstitial-cells
#19
Bo Wang, Guangxia Wei, Baoqing Liu, Xianming Zhou, Hua Xiao, Nianguo Dong, Fei Li
BACKGROUND: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. METHODS: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting...
July 9, 2016: Cardiology
https://www.readbyqxmd.com/read/27392969/inflammation-drives-retraction-stiffening-and-nodule-formation-via-cytoskeletal-machinery-in-a-three-dimensional-culture-model-of-aortic-stenosis
#20
Jina Lim, Arshia Ehsanipour, Jeffrey J Hsu, Jinxiu Lu, Taylor Pedego, Alexander Wu, Chris M Walthers, Linda L Demer, Stephanie K Seidlits, Yin Tintut
In calcific aortic valve disease, the valve cusps undergo retraction, stiffening, and nodular calcification. The inflammatory cytokine, tumor necrosis factor (TNF)-α, contributes to valve disease progression; however, the mechanisms of its actions on cusp retraction and stiffening are unclear. We investigated effects of TNF-α on murine aortic valvular interstitial cells (VICs) within three-dimensional, free-floating, compliant, collagen hydrogels, simulating their natural substrate and biomechanics. TNF-α increased retraction (percentage of diameter), stiffness, and formation of macroscopic, nodular structures with calcification in the VIC-laden hydrogels...
September 2016: American Journal of Pathology
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