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https://www.readbyqxmd.com/read/29679571/metformin-ameliorates-tgf-%C3%AE-1-induced-osteoblastic-differentiation-of-human-aortic-valve-interstitial-cells-by-inhibiting-%C3%AE-catenin-signaling
#1
Liu Fayuan, Chu Chong, Wei Qinyu, Shi Jiawei, Li Huadong, Dong Nianguo
Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-β1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29618659/mesenchymal-tnfr2-promotes-the-development-of-polyarthritis-and-comorbid-heart-valve-stenosis
#2
Maria Sakkou, Panagiotis Chouvardas, Lydia Ntari, Alejandro Prados, Kristin Moreth, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Maria C Denis, Niki Karagianni, George Kollias
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in arthritis has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific role of Tnfr2 in the TnfΔARE mouse model of SpA in arthritis and heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 signaling in resident synovial fibroblasts (SFs) and valvular interstitial cells (VICs) is detrimental for both pathologies, pointing to common cellular mechanisms...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29614432/pathological-significance-of-lipoprotein-a-in-aortic-valve-stenosis
#3
Bin Yu, Kashif Khan, Qutayba Hamid, Ahmad Mardini, Ateeque Siddique, Louis Philippe Aguilar-Gonzalez, Georges Makhoul, Hossny Alaws, Jacques Genest, George Thanassoulis, Renzo Cecere, Adel Schwertani
BACKGROUND AND AIMS: Aortic valve stenosis (AVS) affects a significant percentage of our elderly population and younger subjects with familial hypercholesterolemia. Lipoprotein(a) [Lp(a)] has been associated with AVS in recent genetic studies. The purpose of this study was to determine the effects of Lp(a) on human aortic valve interstitial cells (HAVICs), and to identify apolipoproteins and phospholipids in diseased human aortic valves. METHODS: We examined the effects of Lp(a) on HAVICs mineralization and oxidant formation...
March 15, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29594151/advances-in-pathophysiology-of-calcific-aortic-valve-disease-propose-novel-molecular-therapeutic-targets
#4
Alexia Hulin, Alexandre Hego, Patrizio Lancellotti, Cécile Oury
Calcific Aortic Valve Disease (CAVD) is the most common heart valve disease and its incidence is expected to rise with aging population. No medical treatment so far has shown slowing progression of CAVD progression. Surgery remains to this day the only way to treat it. Effective drug therapy can only be achieved through a better insight into the pathogenic mechanisms underlying CAVD. The cellular and molecular events leading to leaflets calcification are complex. Upon endothelium cell damage, oxidized LDLs trigger a proinflammatory response disrupting healthy cross-talk between valve endothelial and interstitial cells...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29592957/intra-cardiac-release-of-extracellular-vesicles-shapes-inflammation-following-myocardial-infarction
#5
Xavier Loyer, Ivana Zlatanova, Cécile Devue, Min Yin, Kiave-Yune Howangyin, Phatchanat Klaihmon, Coralie L Guerin, Marouane Kheloufi, José Vilar, Konstantinos Zannis, Bernd K Fleischmann, Do Won Hwang, Jongmin Park, Hakho Lee, Philippe Menasche, Jean-Sébastien Silvestre, Chantal M Boulanger
<u>Rationale:</u> A rapid and massive influx of inflammatory cells occurs into ischemic area following myocardial infarction, resulting in local release of cytokines and growth factors. Yet, the mechanisms regulating their production are not fully explored. The release of extracellular vesicles (EV) in the interstitial space curbs important biological functions, including inflammation, and influences the development of cardiovascular diseases. So far, there is no evidence for in situ release of cardiac EVs following myocardial infarction...
March 28, 2018: Circulation Research
https://www.readbyqxmd.com/read/29588317/spatiotemporal-multi-omics-mapping-generates-a-molecular-atlas-of-the-aortic-valve-and-reveals-networks-driving-disease
#6
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
https://www.readbyqxmd.com/read/29558203/enzymes-of-the-purinergic-signaling-system-exhibit-diverse-effects-on-the-degeneration-of-valvular-interstitial-cells-in-a-3-d-microenvironment
#7
Andreas Weber, Mareike Barth, Jessica Isabel Selig, Silja Raschke, Konstantinos Dakaras, Alexander Hof, Julia Hesse, Jürgen Schrader, Artur Lichtenberg, Payam Akhyari
Calcific aortic valve disease is an active disease process with lipoprotein deposition, chronic inflammation, and progressive leaflet degeneration. Expression of ectonucleotidases, a group of membrane-bound enzymes that regulate the metabolism of ATP and its metabolites, may coregulate the degeneration process of valvular interstitial cells (VICs). The aim of this study was to investigate the role of the enzymes of the purinergic system in the degeneration process of VICs. Ovine VICs were cultivated in vitro under different prodegenerative conditions and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39)/ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5'-nucleotidase (CD73), as well as with adenosine and adenosine receptor agonists...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29539583/increased-calcific-aortic-valve-disease-in-response-to-a-diabetogenic-procalcific-diet-in-the-ldlr-apob-100-100-mouse-model
#8
Marta Scatena, Melissa F Jackson, Mei Y Speer, Elizabeth M Leaf, Mary C Wallingford, Cecilia M Giachelli
OBJECTIVE: Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis (AS) and cardiac insufficiency. Patients with type II diabetes mellitus (T2DM) are at heightened risk for CAVD, and their valves have greater calcification than nondiabetic valves. No drugs to prevent or treat CAVD exist, and animal models that might help identify therapeutic targets are sorely lacking. To develop an animal model mimicking the structural and functional features of CAVD in people with T2DM, we tested a diabetogenic, procalcific diet and its effect on the incidence and severity of CAVD and AS in the, LDLr-/- ApoB100/100 mouse model...
February 15, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29505894/human-ipsc-derived-mesenchymal-stem-cells-encapsulated-in-pegda-hydrogels-mature-into-valve-interstitial-like-cells
#9
Aline L Y Nachlas, Siyi Li, Rajneesh Jha, Monalisa Singh, Chunhui Xu, Michael E Davis
Despite recent advances in tissue engineered heart valves (TEHV), a major challenge is identifying a cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. This study demonstrates that induced pluripotent stem cells (iPSC)-derived mesenchymal stem cells (iMSCs) can be derived from iPSCs using a feeder-free protocol and then further matured into VICs by encapsulation within 3D hydrogels...
March 2, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29505892/crystallinity-of-hydroxyapatite-drives-myofibroblastic-activation-and-calcification-in-aortic-valves
#10
Jennifer M Richards, Jennie A M R Kunitake, Heather B Hunt, Alexa N Wnorowski, Debra W Lin, Adele L Boskey, Eve Donnelly, Lara A Estroff, Jonathan T Butcher
Calcific aortic valve disease (CAVD) is an inexorably degenerative pathology characterized by progressive calcific lesion formation on the valve leaflets. The interaction of valvular cells in advanced lesion environments is not well understood yet highly relevant as clinically detectable CAVD exhibits calcifications composed of non-stoichiometric hydroxyapatite (HA). In this study, Fourier transform infrared spectroscopic imaging was used to spatially analyze mineral properties as a function of disease progression...
March 2, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29475857/comorbid-tnf-mediated-heart-valve-disease-and-chronic-polyarthritis-share-common-mesenchymal-cell-mediated-aetiopathogenesis
#11
Lydia Ntari, Maria Sakkou, Panagiotis Chouvardas, Iordanis Mourouzis, Alejandro Prados, Maria C Denis, Niki Karagianni, Constantinos Pantos, George Kollias
OBJECTIVES: Patients with rheumatoid arthritis and spondyloarthritisshow higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) arthritis model develops tumour necrosis factor (TNF)-driven and mesenchymalsynovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this model develops, similarly to human patients, comorbid heart pathology and explore cellular and molecular mechanisms linking arthritis to cardiac comorbidities. METHODS: Histopathological analysis and echocardiographic evaluation of cardiac function were performed in the Tg197 model...
February 23, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29471937/reverse-myocardial-remodeling-following-valve-replacement-in-patients-with-aortic-stenosis
#12
Thomas A Treibel, Rebecca Kozor, Rebecca Schofield, Giulia Benedetti, Marianna Fontana, Anish N Bhuva, Amir Sheikh, Begoña López, Arantxa González, Charlotte Manisty, Guy Lloyd, Peter Kellman, Javier Díez, James C Moon
BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2 /m2 ) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test...
February 27, 2018: Journal of the American College of Cardiology
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
#13
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), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates 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...
March 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348122/macrophage-transitions-in-heart-valve-development-and-myxomatous-valve-disease
#14
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...
March 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
#15
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, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p < 0...
April 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
#16
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
#17
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
#18
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...
February 2018: 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
#19
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
#20
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...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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