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Modelling heart valve growth

Diana M Ropcke, Christine Ilkjaer, Marcell J Tjornild, Soren N Skov, Steffen Ringgaard, Vibeke E Hjortdal, Sten L Nielsen
OBJECTIVES: Tricuspid valve reconstruction using small intestinal submucosal extracellular matrix (ECM) designed as a tube graft is possible in severe valve pathology. Using cardiac magnetic resonance imaging (MRI) and digital photograph imaging, valves were evaluated after 6 months in a porcine model. METHODS: Ten 60 kg pigs received a tricuspid valve tube graft. A baseline MRI was performed after 2 weeks ( n  = 8). A follow-up MRI was performed in three of five 6 months' survivors to assess function and haemodynamics of the tricuspid tube graft...
February 27, 2017: Interactive Cardiovascular and Thoracic Surgery
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
Christian Dullin, Roser Ufartes, Emanuel Larsson, Sabine Martin, Marcio Lazzarini, Giuliana Tromba, Jeannine Missbach-Guentner, Diana Pinkert-Leetsch, Dörthe M Katschinski, Frauke Alves
The small size of the adult and developing mouse heart poses a great challenge for imaging in preclinical research. The aim of the study was to establish a phosphotungstic acid (PTA) ex-vivo staining approach that efficiently enhances the x-ray attenuation of soft-tissue to allow high resolution 3D visualization of mouse hearts by synchrotron radiation based μCT (SRμCT) and classical μCT. We demonstrate that SRμCT of PTA stained mouse hearts ex-vivo allows imaging of the cardiac atrium, ventricles, myocardium especially its fibre structure and vessel walls in great detail and furthermore enables the depiction of growth and anatomical changes during distinct developmental stages of hearts in mouse embryos...
2017: PloS One
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
Agnieszka A Książek, Katharyn J Mitchell, Nikola Cesarovic, Colin C Schwarzwald, Simon P Hoerstrup, Benedikt Weber
BACKGROUND: Bioengineered living autologous valves with remodeling and growth capacity represent a promising concept for future cardiac and venous valve repair. A meticulous understanding of the mechanisms involved in recellularization and remodeling is essential for the safe and efficient clinical translation of this technology. In this context, the first investigations of bioengineered vascular grafts in immune-incompetent or transgenic rodents represented an important step. However, the in-vivo assessment of bioengineered synthetic scaffold-based (biodegradable) valve replacements in rodent models has not been achieved to date...
May 2016: Journal of Heart Valve Disease
Rosa Di Liddo, Paola Aguiari, Silvia Barbon, Thomas Bertalot, Amit Mandoli, Alessia Tasso, Sandra Schrenk, Laura Iop, Alessandro Gandaglia, Pier Paolo Parnigotto, Maria Teresa Conconi, Gino Gerosa
Considerable progress has been made in recent years toward elucidating the correlation among nanoscale topography, mechanical properties, and biological behavior of cardiac valve substitutes. Porcine TriCol scaffolds are promising valve tissue engineering matrices with demonstrated self-repopulation potentiality. In order to define an in vitro model for investigating the influence of extracellular matrix signaling on the growth pattern of colonizing blood-derived cells, we cultured circulating multipotent cells (CMC) on acellular aortic (AVL) and pulmonary (PVL) valve conduits prepared with TriCol method and under no-flow condition...
2016: International Journal of Nanomedicine
Peter E Hammer, Erin G Roberts, Sitaram M Emani, Pedro J Del Nido
OBJECTIVES: Neither heart valve repair methods nor current prostheses can accommodate patient growth. Normal aortic and pulmonary valves have 3 leaflets, and the goal of valve repair and replacement is typically to restore normal 3-leaflet morphology. However, mammalian venous valves have bileaflet morphology and open and close effectively over a wide range of vessel sizes. We propose that they might serve as a model for pediatric heart valve reconstruction and replacement valve design...
February 2017: Journal of Thoracic and Cardiovascular Surgery
Tilly Eldridge, Łukasz Łangowski, Nicola Stacey, Friederike Jantzen, Laila Moubayidin, Adrien Sicard, Paul Southam, Richard Kennaway, Michael Lenhard, Enrico S Coen, Lars Østergaard
Fruits exhibit a vast array of different 3D shapes, from simple spheres and cylinders to more complex curved forms; however, the mechanism by which growth is oriented and coordinated to generate this diversity of forms is unclear. Here, we compare the growth patterns and orientations for two very different fruit shapes in the Brassicaceae: the heart-shaped Capsella rubella silicle and the near-cylindrical Arabidopsis thaliana silique. We show, through a combination of clonal and morphological analyses, that the different shapes involve different patterns of anisotropic growth during three phases...
September 15, 2016: Development
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
Fraser D Rubens, Yen-Yen Gee, Janet M C Ngu, Li Chen, Ian G Burwash
OBJECTIVES: We sought to assess the effect of 2 contemporary pericardial valves on left ventricular mass regression and clinical outcomes after aortic valve replacement (AVR) in patients with aortic stenosis (AS). METHODS: Patients were followed postoperatively in a dedicated valve clinic. A propensity score was derived for each patient and used to adjust all analyses. Longitudinal analysis was performed using a repeated measures growth curve model. Survival analysis was assessed with a Cox proportional hazards model...
November 2016: Journal of Thoracic and Cardiovascular Surgery
Ling Qiuyang, Wu Ting, Ye Ting, Su Zhaoliang, Zong Gangjun
OBJECTIVE: To establish human heart valve interstitial cells calcification culture model in vitro, and observe the effect of bone morphogenetic protein-2 (BMP-2) on calcification of human heart valve interstitial cells. METHODS: Human heart valve interstitial cells were cultured in vitro, and divided into control group: cells were cultured in conventional media plus recombinant human BMP-2 treatment and experimental group: besides above treaments, calcification inducers ( recombinant human BMP-2, β-glycerophosphate, L-ascorbic acid, dexamethasone) were added to the culture media...
August 2015: Zhonghua Xin Xue Guan Bing za Zhi
Mehdi Jahandardoost, Guy Fradet, Hadi Mohammadi
To date, to the best of the authors' knowledge, in almost all of the studies performed around the hemodynamics of bileaflet mechanical heart valves, a heart rate of 70-72 beats/min has been considered. In fact, the heart rate of ~72 beats/min does not represent the entire normal physiological conditions under which the aortic or prosthetic valves function. The heart rates of 120 or 50 beats/min may lead to hemodynamic complications, such as plaque formation and/or thromboembolism in patients. In this study, the hemodynamic performance of the bileaflet mechanical heart valves in a wide range of normal and physiological heart rates, that is, 60-150 beats/min, was studied in the opening phase...
March 2016: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
Yusuke Sakamoto, Rachel M Buchanan, Michael S Sacks
Heart valve interstitial cells (VICs) play a critical role in the maintenance and pathophysiology of heart valve tissues. Normally quiescent in the adult, VICs can become activated in periods of growth and disease. When activated, VICs exhibit increased levels of cytokines and extracellular matrix (ECM) synthesis, and upregulated expression and strong contraction of α-smooth muscle actin (α-SMA) fibers. However, it remains unknown how expression and contraction of the α-SMA fibers, which vary among different VIC types, contribute to the overall VIC mechanical responses, including the nucleus and cytoskeleton contributions...
February 2016: Journal of the Mechanical Behavior of Biomedical Materials
Apinya Bharmanee, Kathleen Zelin, Yamuna Sanil, Pooja Gupta, Peter P Karpawich
BACKGROUND: Standard, 5-7-Fr diameter pacing leads (PLs) can adversely affect atrioventricular valve (AVV) and venous (superior vena cava [SVC], innominate [INN]) integrities. Although chronic pacing/sensing performances have been reported on the steroid-eluting, lumenless, 4.1-Fr PL (Model 3830, Medtronic Inc., Minneapolis, MN, USA), comparative valve and venous effects are largely unknown. METHODS: Patients (n = 134) were divided into two PL groups: Group 1 (n = 65, Model 3830) and Group 2 (n = 69, various 5-7 Fr models) and followed up to 9 years postimplant...
November 2015: Pacing and Clinical Electrophysiology: PACE
Daniel S Puperi, Liezl R Balaoing, Ronan W O'Connell, Jennifer L West, K Jane Grande-Allen
Physiologically relevant in vitro models are needed to study disease progression and to develop and screen potential therapeutic interventions for disease. Heart valve disease, in particular, has no early intervention or non-invasive treatment because there is a lack of understanding the cellular mechanisms which lead to disease. Here, we establish a novel, customizable synthetic hydrogel platform that can be used to study cell-cell interactions and the factors which contribute to valve disease. Spatially localized cell adhesive ligands bound in the scaffold promote cell growth and organization of valve interstitial cells and valve endothelial cells in 3D co-culture...
October 2015: Biomaterials
Elodie Mintet, Emilie Rannou, Valérie Buard, Gail West, Olivier Guipaud, Georges Tarlet, Jean-Christophe Sabourin, Marc Benderitter, Claudio Fiocchi, Fabien Milliat, Agnès François
The endothelial-to-mesenchymal transition (EndoMT) is a crucial cellular process during heart development necessary to the formation of cardiac valves. This embryonic process reappears in several pathological situations, such as vascular injury or organ fibrosis of various etiologies, as a mediator of extracellular matrix-producing cells. Because radiation induces both vascular damage and fibrosis, we investigated whether radiation exposure induces EndoMT in primary human intestinal microvascular endothelial cells (HIMECs) and whether EndoMT contributes to radiation-induced rectal damage in humans and in a preclinical model of radiation proctitis in mice...
September 2015: American Journal of Pathology
Zahra Vahabi, Rasool Amirfattahi
Aorta is formed in a dynamic environment which gives rise to imbalances between many forces that tend to extend the diameter and length. Furthermore, internal forces tend to resist this extension. Impedance tomography can show this imbalance to stimulate the stenosis of aortic valve, growth of the elastic, collagen and to effectively reduce the stresses in the underlying tissue. In blood flow, auscultation noises occurred and in the echocardiography decrease in left ventricular ejection speed can be observed...
April 2015: Journal of Medical Signals and Sensors
Shogo Shimada, Christian Robles, Ben M W Illigens, Alejandra M Casar Berazaluce, Pedro J del Nido, Ingeborg Friehs
BACKGROUND: Endocardial fibroelastosis (EFE), characterized by a diffuse endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Recent advances in fetal imaging indicate that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome (HLHS). In this study, we developed an animal model of EFE by introducing this human fetal LV morphopathology to an immature rat heart...
2015: BioMed Research International
Brian R Lindman, Jared G Breyley, Joel D Schilling, Anna M Vatterott, Alan Zajarias, Hersh S Maniar, Ralph J Damiano, Marc R Moon, Jennifer S Lawton, Brian F Gage, Marc A Sintek, Alejandro Aquino, Christopher L Holley, Neil M Patel, Cassandra Lawler, John M Lasala, Eric Novak
OBJECTIVE: In heart failure populations without aortic stenosis (AS), the prognostic utility of multiple biomarkers in addition to clinical factors has been demonstrated. We aimed to determine whether multiple biomarkers of cardiovascular stress are associated with mortality in patients with AS undergoing aortic valve replacement (AVR) independent of clinical factors. METHODS: From a prospective registry of patients with AS, 345 participants who were referred for and treated with AVR (transcatheter (n=183) or surgical (n=162)) were included...
September 2015: Heart: Official Journal of the British Cardiac Society
Boyang Su, Foad Kabinejadian, Hui Qun Phang, Gideon Praveen Kumar, Fangsen Cui, Sangho Kim, Ru San Tan, Jimmy Kim Fatt Hon, John Carson Allen, Hwa Liang Leo, Liang Zhong
This work presents a numerical simulation of intraventricular flow after the implantation of a bileaflet mechanical heart valve at the mitral position. The left ventricle was simplified conceptually as a truncated prolate spheroid and its motion was prescribed based on that of a healthy subject. The rigid leaflet rotation was driven by the transmitral flow and hence the leaflet dynamics were solved using fluid-structure interaction approach. The simulation results showed that the bileaflet mechanical heart valve at the mitral position behaved similarly to that at the aortic position...
2015: PloS One
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