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Florian Schlotter, Arda Halu, Shinji Goto, Mark C Blaser, Simon C Body, Lang H Lee, Hideyuki Higashi, Daniel M DeLaughter, Joshua D Hutcheson, Payal Vyas, Tan Pham, Maximillian A Rogers, Amitabh Sharma, Christine E Seidman, Joseph Loscalzo, Jonathan G Seidman, Masanori Aikawa, Sasha A Singh, Elena Aikawa
Background -No pharmacological therapy exists for calcific aortic valve disease (CAVD), which confers a dismal prognosis without invasive valve replacement. The search for therapeutics and early diagnostics is challenging since CAVD presents in multiple pathological stages. Moreover, it occurs in the context of a complex, multi-layered tissue architecture, a rich and abundant extracellular matrix phenotype, and a unique, highly plastic and multipotent resident cell population. Methods -A total of 25 human stenotic aortic valves obtained from valve replacement surgeries were analyzed by multiple modalities, including transcriptomics and global unlabeled and label-based tandem-mass-tagged proteomics...
March 27, 2018: Circulation
Ying Lei, Shirin Masjedi, Zannatul Ferdous
In aortic valves, biaxial cyclic stretch is known to modulate cell differentiation, extracellular matrix (ECM) synthesis and organization. We designed a novel bioreactor that can apply independent and precise stretch along radial and circumferential directions in a tissue culture environment. While this bioreactor can be used for either native or engineered tissues, this study determined matrix remodeling and strain distribution of aortic cusps after culturing under biaxial stretch for 14 days. The contents of collagen and glycosaminoglycans were determined using standard biochemical assays and compared with fresh controls...
November 2017: Journal of the Mechanical Behavior of Biomedical Materials
Katsutoshi Miura, Hideki Katoh
The aim of this study was to reveal the pathogenesis of aortic stenosis (AS) and regurgitation (AR) by comparing differences in mechanical and biochemical alterations. We applied scanning acoustic microscopy (SAM) to measure the speed of sound (SOS) through valves to estimate the elasticity and monitor sensitivity to protease treatment, as the SOS is correlated with the stiffness of materials, which is reduced after digestion by proteases. The fibrosa of both the AS and AR groups were stiffer than the fibrosa of the normal group...
2016: BioMed Research International
Swetha Rathan, Casey J Ankeny, Sivakkumar Arjunon, Zannatul Ferdous, Sandeep Kumar, Joan Fernandez Esmerats, Jack M Heath, Robert M Nerem, Ajit P Yoganathan, Hanjoong Jo
Aortic valve (AV) calcification is an inflammation driven process that occurs preferentially in the fibrosa. To explore the underlying mechanisms, we investigated if key microRNAs (miRNA) in the AV are differentially expressed due to disturbed blood flow (oscillatory shear (OS)) experienced by the fibrosa compared to the ventricularis. To identify the miRNAs involved, endothelial-enriched RNA was isolated from either side of healthy porcine AVs for microarray analysis. Validation using qPCR confirmed significantly higher expression of 7 miRNAs (miR-100, -130a, -181a/b, -199a-3p, -199a-5p, and -214) in the fibrosa versus the ventricularis...
May 6, 2016: Scientific Reports
Tomohiro Saito, Katharina Wassilew, Boris Gorodetski, Julia Stein, Volkmar Falk, Thomas Krabatsch, Evgenij Potapov
BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVAD) may induce pathological changes to the aortic wall and aortic valve. We assessed histological changes in the relevant anatomic structures exposed to continuous flow over time and compared the histological results with clinical features in patients supported with CF-LVAD. METHODS AND RESULTS: A retrospective histological analysis was performed of 38 explanted hearts supported with CF-LVAD from patients who received heart transplantation between July 2003 and February 2014...
May 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Daphne van Geemen, Ana L F Soares, Pim J A Oomen, Anita Driessen-Mol, Marloes W J T Janssen-van den Broek, Antoon J van den Bogaerdt, Ad J J C Bogers, Marie-José T H Goumans, Frank P T Baaijens, Carlijn V C Bouten
There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed...
2016: PloS One
Tomoki Ushijima, Yoshihisa Tanoue, Tomomi Ide, Shinji Okano, Yoshinao Oda, Ryuji Tominaga
A 31-year-old woman underwent implantation of a DuraHeart left ventricular assist device as bridge to transplantation. Aortic insufficiency was not observed before implantation but developed after implantation and became severe approximately 2 years later. Macroscopically, the aortic valve excised during heart transplantation showed no morphologic alteration. Microscopically, the collagen fibers in the fibrosa layer and the elastic fibers in the ventricularis layer of the valve leaflets were reduced in number, with irregular arrangement...
February 2016: Annals of Thoracic Surgery
K Cao, M Bukač, P Sucosky
The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid-structure interaction modeling. An arbitrary Lagrangian-Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure...
2016: Computer Methods in Biomechanics and Biomedical Engineering
Chung-Hao Lee, Christopher A Carruthers, Salma Ayoub, Robert C Gorman, Joseph H Gorman, Michael S Sacks
Within each of the four layers of mitral valve (MV) leaflet tissues there resides a heterogeneous population of interstitial cells that maintain the structural integrity of the MV tissue via protein biosynthesis and enzymatic degradation. There is increasing evidence that tissue stress-induced MV interstitial cell (MVIC) deformations can have deleterious effects on their biosynthetic states that are potentially related to the reduction of tissue-level maintenance and to subsequent organ-level failure. To better understand the interrelationships between tissue-level loading and cellular responses, we developed the following integrated experimental-computational approach...
May 21, 2015: Journal of Theoretical Biology
J Stasiak, J Brubert, M Serrani, A Talhat, F De Gaetano, M L Costantino, G D Moggridge
Load-bearing tissues are composite materials that depend strongly on anisotropic fibre arrangement to maximise performance. One such tissue is the heart valve, with orthogonally arranged fibrosa and ventricularis layers. Their function is to maintain mechanical stress while being resilient. It is postulated that while one layer bears the applied stress, the orthogonal layer helps to regenerate the microstructure when the load is released. The present paper describes changes in the microstructure of a block copolymer with cylindrical morphology, having a bio-inspired microstructure of anisotropic orthogonally oriented layers, under uniaxial strain...
April 28, 2015: Soft Matter
Jaroslava Halper
Proteoglycans consist of a protein core to which at least one glycosaminoglycan chain is attached. They play important roles in the physiology and biomechanical function of tendons, ligaments and cardiovascular system through their involvement in regulation of assembly and maintenance of extracellular matrix, and as they participate in cell proliferation through their interactions with growth factors. They can be divided into two main groups of small and large proteoglycans. The small proteoglycans are also known as small leucine-rich proteoglycans (or SLRPs) which are encoded by 17 genes and are further subclassified into Classes I-V...
2014: Advances in Experimental Medicine and Biology
Chelsea T McIntosh, James N Warnock
BACKGROUND AND AIM OF THE STUDY: Aortic valve ectopic calcification occurs exclusively on the fibrosa surface. This may be due to the distinct mechanical environments on either side of the valve, or to the existence of unique, side-specific endothelial sub-phenotypes. The study aim was to determine if side-specific endothelial cells (ECs) would differentially express cell-cell and cell-matrix adhesion molecules in response to elevated levels of equibiaxial tensile strain. METHODS: Side-specific porcine aortic valve ECs were isolated and strained at 10% or 20% using a Flexcell 4000T for 24 h, and compared to static controls...
September 2013: Journal of Heart Valve Disease
Ling Sun, Nalini M Rajamannan, Philippe Sucosky
Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between cardiovascular risk factors, molecular signaling networks and hemodynamic cues. While earlier studies demonstrated that alterations in fluid shear stress (FSS) on the fibrosa could trigger inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. This knowledge could be critical to the elucidation of key CAVD risk factors such as congenital valve defects, aging and hypertension, which are known to generate FSS disturbances...
2013: PloS One
Svenja Hinderer, Jan Seifert, Miriam Votteler, Nian Shen, Johannes Rheinlaender, Tilman E Schäffer, Katja Schenke-Layland
Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet...
February 2014: Biomaterials
Rachel M Buchanan, Michael S Sacks
While the mechanical behaviors of the fibrosa and ventricularis layers of the aortic valve (AV) leaflet are understood, little information exists on their mechanical interactions mediated by the GAG-rich central spongiosa layer. Parametric simulations of the interlayer interactions of the AV leaflets in flexure utilized a tri-layered finite element (FE) model of circumferentially oriented tissue sections to investigate inter-layer sliding hypothesized to occur. Simulation results indicated that the leaflet tissue functions as a tightly bonded structure when the spongiosa effective modulus was at least 25 % that of the fibrosa and ventricularis layers...
August 2014: Biomechanics and Modeling in Mechanobiology
Jerald Moon, Fariborz Alipour
OBJECTIVES: Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. METHODS: Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds...
September 2013: Annals of Otology, Rhinology, and Laryngology
Joseph E Dohar, Laura L Greenberg, Rhona I Galera
OBJECTIVE: There's no greater challenge in pediatric laryngology than diagnosis and treatment of chronic dysphonia following laryngotracheal reconstruction of acquired subglottic stenosis. Videolaryngoscopy with stroboscopy provides incomparable diagnostic information to fiberoptic endoscopy. Unfortunately, this pediatric subpopulation which would benefit the most from videolaryngoscopy with stroboscopy infrequently does. We present the unique videolaryngostroboscopic patterns with their diagnostic and treatment implications in this complex population...
May 2013: International Journal of Pediatric Otorhinolaryngology
Christopher A Carruthers, Christina M Alfieri, Erinn M Joyce, Simon C Watkins, Katherine E Yutzey, Michael S Sacks
The semilunar (aortic and pulmonary) heart valves function under dramatically different hemodynamic environments, and have been shown to exhibit differences in mechanical properties, extracellular matrix (ECM) structure, and valve interstitial cell (VIC) biosynthetic activity. However, the relationship between VIC function and the unique micromechanical environment in each semilunar heart valve remains unclear. In the present study, we quantitatively compared porcine semilunar mRNA expression of primary ECM constituents, and layer- and valve-specific VIC-collagen mechanical interactions under increasing transvalvular pressure (TVP)...
September 1, 2012: Cellular and Molecular Bioengineering
Najlah Kochtebane, Christine Choqueux, Jean-Baptiste Michel, Marie-Paule Jacob
Valvular heart diseases represent an important public health burden. With the decrease in the incidence of rheumatic heart disease, calcific aortic stenosis has now become the most common valvular disease in Western countries. Its prevalence increases with age, such that its affects about 4% of the elderly population and it is the most common motive for valve replacement. Several tissue abnormalities were observed in aortic valves from patients suffering from aortic stenosis: presence of large calcium deposits, inflammatory cells, lipids, and neocapillaries as well as extracellular matrix remodeling...
2012: Biologie Aujourd'hui
Nwanmegha Young, Mikhail Wadie, Clarence T Sasaki
OBJECTIVES: We sought to examine the neuromuscular basis for ventricular fold function. The primary function of the ventricular folds is to assist in the regulation of intra-abdominal and intrathoracic pressure. They also influence phonation in the setting of vocal fold paralysis or ventricular dysphonia, or after partial laryngectomy. The neuromuscular basis of true vocal fold function has been well studied; however, its neuromuscular correlates in the ventricular folds are ambiguous...
May 2012: Annals of Otology, Rhinology, and Laryngology
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