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https://www.readbyqxmd.com/read/29026447/epigenome-alterations-in-aortic-valve-stenosis-and-its-related-left-ventricular-hypertrophy
#1
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
https://www.readbyqxmd.com/read/29016735/lncrna-tug1-sponges-mir-204-5p-to-promote-osteoblast-differentiation-through-upregulating-runx2-in-aortic-valve-calcification
#2
Cong Yu, Lifu Li, Fei Xie, Shichao Guo, Fayuan Liu, Nianguo Dong, Yongjun Wang
Aims: Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a vital role in cardiovascular physiology and pathology. Although the lncRNA TUG1 is implicated in atherosclerosis, its function in calcific aortic valve disease (CAVD) remains unknown. Methods and Results: In this study, we found that TUG1 was highly expressed in human aortic valves and primary valve interstitial cells (VICs). Moreover, TUG1 knockdown induced inhibition of osteoblast differentiation in CAVD both in vitro and in vivo ...
September 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28985862/autophagy-negatively-regulates-pro-osteogenic-activity-in-human-aortic-valve-interstitial-cells
#3
Xin-Sheng Deng, Xianzhong Meng, Neil Venardos, Rui Song, Katsuhiro Yamanaka, David Fullerton, James Jaggers
BACKGROUND: Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro-osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs. MATERIALS AND METHODS: AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques...
October 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28922978/6-year-old-sheep-as-a-clinically-relevant-large-animal-model-for-aortic-valve-replacement-using-tissue-engineered-grafts-based-on-decellularized-allogenic-matrix
#4
Karolina Theodoridis, Igor Tudorache, Serghei Cebotari, Tanja Meyer, Alexandru Calistru, Samir Sarikouch, Cristoph Bara, Axel Haverich, Andres Hilfiker
Tissue-engineered (TE) grafts based on decellularized grafts have shown very promising results in preclinical and clinical studies. However, in animal models valves have either been tested in juvenile models or in the clinically less relevant pulmonary valve position. In this study, we tested the grafts in the aortic valve (AV) position of 6-year old sheep, as geriatric patients in need of an aortic valve substitute due to calcification are the largest patient group benefiting from TE grafts. Decellularized AV (n=4) and decellularized AV additionally re-endothelialized with autologous cells (n=3) were implanted in the aortic valve position of 6-year-old female sheep...
September 19, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28912209/valve-interstitial-cells-the-key-to-understanding-the-pathophysiology-of-heart-valve-calcification
#5
Arkady Rutkovskiy, Anna Malashicheva, Gareth Sullivan, Maria Bogdanova, Anna Kostareva, Kåre-Olav Stensløkken, Arnt Fiane, Jarle Vaage
No abstract text is available yet for this article.
September 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28891115/deficiency-of-ccaat-enhancer-binding-protein-homologous-protein-chop-prevents-diet-induced-aortic-valve-calcification-in%C3%A2-vivo
#6
Zhejun Cai, Baoqing Liu, Jia Wei, Zurong Fu, Yidong Wang, Yaping Wang, Jian Shen, Liangliang Jia, Shengan Su, Xiaoya Wang, Xiaoping Lin, Han Chen, Fei Li, Jian'an Wang, Meixiang Xiang
Aortic valve (AoV) calcification is common in aged populations. Its subsequent aortic stenosis has been linked with increased morbidity, but still has no effective pharmacological intervention. Our previous data show endoplasmic reticulum (ER) stress is involved in AoV calcification. Here, we investigated whether deficiency of ER stress downstream effector CCAAT/enhancer-binding protein homology protein (CHOP) may prevent development of AoV calcification. AoV calcification was evaluated in Apoe(-/-) mice (n = 10) or in mice with dual deficiencies of ApoE and CHOP (Apoe(-/-) CHOP(-/-) , n = 10) fed with Western diet for 24 weeks...
September 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28890780/recellularization-of-decellularized-heart-valves-progress-toward-the-tissue-engineered-heart-valve
#7
REVIEW
Mitchell C VeDepo, Michael S Detamore, Richard A Hopkins, Gabriel L Converse
The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28863437/serotonin-and-catecholamines-in-the-development-and-progression-of-heart-valve-diseases
#8
Elliott Goldberg, Juan B Grau, Jacqueline H Fortier, Elisa Salvati, Robert J Levy, Giovanni Ferrari
Heart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling...
July 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28842437/hypoxia-promotes-primitive-glycosaminoglycan-rich-extracellular-matrix-composition-in-developing-heart-valves
#9
Dorothy Amofa, Alexia Hulin, Yuji Nakada, Hesham A Sadek, Katherine E Yutzey
During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation, as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric oxygen, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis are not well-characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells (VICs)...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28821833/microrna-449c-5p-inhibits-osteogenic-differentiation-of-human-vics-through-smad4-mediated-pathway
#10
Rongjian Xu, Min Zhao, Yun Yang, Zhuo Huang, Chunying Shi, Xianglin Hou, Yannan Zhao, Bing Chen, Zhifeng Xiao, Jianzhou Liu, Qi Miao, Jianwu Dai
Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732089/cx47-fine-tunes-the-handling-of-serum-lipids-but-is-dispensable-for-lymphatic-vascular-function
#11
Merlijn J Meens, Issa Kutkut, Viviane Rochemont, Juan Dubrot, Fouad R Kaladji, Amélie Sabine, Oliver Lyons, Stefanie Hendrikx, Jeremiah Bernier-Latmani, Friedemann Kiefer, Alberto Smith, Stéphanie Hugues, Tatiana V Petrova, Brenda R Kwak
Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency...
2017: PloS One
https://www.readbyqxmd.com/read/28620766/phenotype-transformation-of-aortic-valve-interstitial-cells-due-to-applied-shear-stresses-within-a-microfluidic-chip
#12
Xinmei Wang, Joohyung Lee, Mir Ali, Jungkyu Kim, Carla M R Lacerda
Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses...
June 15, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#13
Maximillian A Rogers, Natalia Maldonado, Joshua D Hutcheson, Claudia Goettsch, Shinji Goto, Iwao Yamada, Tyler Faits, Hiromi Sesaki, Masanori Aikawa, Elena Aikawa
RATIONALE: Mitochondrial changes occur during cell differentiation and cardiovascular disease. DRP1 (dynamin-related protein 1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. OBJECTIVE: To examine the effects of osteogenic promoting conditions on DRP1 and whether DRP1 inhibition alters the development of cardiovascular calcification...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28601321/lysophosphatidylcholine-activates-the-akt-pathway-to-upregulate-extracellular-matrix-protein-production-in-human-aortic-valve-cells
#14
Hui Cheng, Qingzhou Yao, Rui Song, Yufeng Zhai, Wei Wang, David A Fullerton, Xianzhong Meng
BACKGROUND: Overproduction of extracellular matrix (ECM) protein by aortic valve interstitial cells (AVICs) plays an important role in valvular sclerosis (thickening) associated with the early pathobiology of aortic stenosis. Accumulation of oxidized low-density lipoprotein (oxLDL) is observed in sclerotic aortic valve and may have a mechanistic role in valvular disease progression. Lysophosphatidylcholine (LysoPC) is a component of oxLDL and has multiple biological activities. This study was to test the hypothesis that oxLDL and LysoPC upregulate ECM protein production in human AVICs...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28546218/adamts5-deficiency-in-calcified-aortic-valves-is-associated-with-elevated-pro-osteogenic-activity-in-valvular-interstitial-cells
#15
Fei Li, Rui Song, Lihua Ao, T Brett Reece, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
OBJECTIVE: Extracellular matrix proteinases are implicated in the pathogenesis of calcific aortic valve disease. The ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) enzyme is secreted, matrix-associated metalloendopeptidase, capable of degrading extracellular matrix proteins, particularly matrilin 2. We sought to determine the role of the ADAMTS5/matrilin 2 axis in mediating the phenotype transition of valvular interstitial cells (VICs) associated with calcific aortic valve disease...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28536843/human-interstitial-cellular-model-in-therapeutics-of-heart-valve-calcification
#16
REVIEW
Caimei He, Hai Tang, Zijian Mei, Nichujie Li, Zhi Zeng, Kwame Oteng Darko, Yulong Yin, Chien-An Andy Hu, Xiaoping Yang
Calcific aortic valve disease is a common, severe heart condition that is currently with no proven, effective drug treatment and requires a surgical valve replacement or an entire heart explanation. Thus, developing novel, targeted therapeutic approaches becomes a major goal for cardiovascular disease research. To achieve this goal, isolated heart valve interstitial cells could be an advanced model to explore molecular mechanisms and measure drug efficacy. Based on this progress, molecular mechanisms that harbor components of  inflammation and fibrosis coupled with proteins, for example, BMP-2, TLRs, RANKL, Osteoprotegerin, have been proposed...
May 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28522163/lncrna-malat1-sponges-mir-204-to-promote-osteoblast-differentiation-of-human-aortic-valve-interstitial-cells-through-up-regulating-smad4
#17
Xiaoxiong Xiao, Tingwen Zhou, Shichao Guo, Chao Guo, Qiao Zhang, Nianguo Dong, Yongjun Wang
BACKGROUND: Emerging evidences have indicated that long non-coding RNAs (lncRNAs) play vital roles in cardiovascular physiology and pathology. The lncRNA MALAT1, a highly abundant and conserved imprinted gene, has been implicated in many cardiovascular diseases. However, the function of MALAT1 in calcific aortic valve disease (CAVD) remains unknown. This study sought to document the function and underlying mechanism of MALAT1 in regulating CAVD. METHODS: Protein level was determined by immunoblotting and immunofluorescence staining...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28516795/a-comprehensive-guide-to-telocytes-and-their-great-potential-in-cardiovascular-system
#18
REVIEW
I Kucybala, P Janas, S Ciuk, W Cholopiak, W Klimek-Piotrowska, M K Holda
Telocytes, a recently discovered type of interstitial cells, have a very distinctive morphology - the small cell body with long extensions, named telopodes. In our review, apart from introducing general aspects of telocytes, we focus on properties, functions and future potential of those cells in cardiovascular system. However, physiological functions of telocytes in cardiovascular system are still regarded as quite enigmatic. Previous studies claim that they play a role in organogenesis and regeneration, bioelectrical signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis and regulation of blood flow...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28488393/in-vitro-analysis-of-early-calcification-in-aortic-valvular-interstitial-cells-using-laser-induced-breakdown-spectroscopy-libs
#19
Seyyed Ali Davari, Shirin Masjedi, Zannatul Ferdous, Dibyendu Mukherjee
Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages...
May 9, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28484097/fabrication-of-a-matrigel-collagen-semi-interpenetrating-scaffold-for-use-in-dynamic-valve-interstitial-cell-culture
#20
Ngoc Lam, Hanh Lam, Nasya Sturdivant, Kartik Balachandran
The study of heart valve homeostatic and disease mechanisms are often limited by the challenges in simulating the in vivo milieu, where valve cells are surrounded by the extracellular matrix in a three dimensional environment and experience multiple dynamic mechanical forces. Type I collagen is typically the most common three dimensional matrix used to culture valve cells in vitro. Unfortunately, this material has poor mechanical behavior due to an inherent propensity to compact significantly, unlike native valve leaflets...
May 9, 2017: Biomedical Materials
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