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Rui Song, David A Fullerton, Lihua Ao, Ke-Seng Zhao, Xianzhong Meng
Calcific aortic valve disease (CAVD) is common in the elderly population, but pharmacological interventions for managing valvular calcification are unavailable. Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) induce pro-osteogenic activation of human aortic valve interstitial cells (AVICs) that play an important role in valvular calcification. However, the molecular mechanism underlying pro-osteogenic activation in AVICs is incompletely understood. Here, we investigated an epigenetic regulatory mechanism in human AVIC pro-osteogenic activation induced by TGF-β1 and BMP-2...
April 4, 2017: Journal of Biological Chemistry
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A Fullerton, Charles A Dinarello, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists...
March 27, 2017: Molecular Medicine
Qingzhou Yao, Rui Song, Lihua Ao, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and over-production of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves over-express growth factor neurotrophin 3 (NT3)...
March 29, 2017: American Journal of Physiology. Cell Physiology
Fei Li, Qingzhou Yao, Lihua Ao, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
Elevated level of blood phosphate (Pi) associated with chronic kidney disease (CKD) is a risk factor of aortic valve calcification. Aortic valve interstitial cells (AVICs) display osteogenic responses to high Pi although the underlying mechanism is incompletely understood. Sox9 is a pro-chondrogenic factor and may play a role in ectopic tissue calcification. Circulating and kidney levels of Klotho are reduced in patients with CKD. We hypothesized that Sox9 mediates high Pi-induced osteogenic responses in human AVICs and that Klotho inhibits the responses...
March 22, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Wenjun Shen, Jianqing Zhou, Chaoyang Wang, Guangze Xu, Ying Wu, Zhaohui Hu
Chronic inflammation and the calcification of aortic valve interstitial cells (AVICs) are the primary etiologies of calcific aortic valve disease (CAVD). However, the underlying mechanism remains to be elucidated. The present study investigated the importance of high mobility group box 1 (HMGB1) via toll‑like receptor 4 (TLR4) for the regulation of inflammation and calcification in AVICs. It was determined that the expression levels of HMGB1 and TLR4 were increased in the calcific region of aortic valves with CAVD...
March 3, 2017: Molecular Medicine Reports
Qingchun Zeng, Rui Song, David A Fullerton, Lihua Ao, Yufeng Zhai, Suzhao Li, Dov B Ballak, Joseph C Cleveland, T Brett Reece, Timothy A McKinsey, Dingli Xu, Charles A Dinarello, Xianzhong Meng
Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Antonella Bonetti, Alberto Della Mora, Magali Contin, Giorgia Gregoraci, Franco Tubaro, Maurizio Marchini, Fulvia Ortolani
Valve dystrophic calcification is a common disorder affecting normophosphatemic subjects. Here, cultured aortic valve interstitial cells (AVICs) were treated 3 to 28 days with phosphate (Pi) concentrations spanning the normal range in humans (0.8, 1.3, and 2.0 mM) alone or supplemented with proinflammatory stimuli to assess possible priming of dystrophic-like calcification. Compared with controls, spectrophotometric analyses revealed marked increases in calcium amounts and alkaline phosphatase activity for 2...
March 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Qiong Zhan, Rui Song, Fei Li, Lihua Ao, Qingchun Zeng, Dingli Xu, David A Fullerton, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic inflammatory condition and the inflammatory responses of aortic valve interstitial cells (AVICs) play a critical role in the disease progression. Double-stranded RNA (dsRNA) released from damaged or stressed cells is pro-inflammatory and may contribute to the mechanism of chronic inflammation observed in diseased aortic valves. The objective of this study is to determine the effect of dsRNA on AVIC inflammatory responses and the underlying mechanism...
January 4, 2017: American Journal of Physiology. Cell Physiology
Bo Wang, Zhejun Cai, Baoqing Liu, Zongtao Liu, Xianming Zhou, Nianguo Dong, Fei Li
Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum (ER) stress have been shown to be involved in calcific aortic valve disease (CAVD). However, the association between RAGE and ER stress remains unknown in the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE deficiency alleviates aortic valve calcification via the inhibition of ER stress. Up-regulation of RAGE and ER stress markers in calcified human aortic valves were confirmed by immunoblotting. Aortic valve calcification was evaluated in atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE and RAGE (ApoE(-/-)RAGE(-/-)) fed with high cholesterol diet for 24weeks...
December 24, 2016: Biochimica et Biophysica Acta
Zhimin Fu, Bin Luo, Mingpeng Li, Bin Peng, Zheng Wang
We aimed to explore the effects of raloxifene (RAL) on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs). Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value) of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group...
2016: BioMed Research International
Rami O Tadros, Melissa L Tardiff, Peter L Faries, Michael Stoner, Chien Yi M Png, David Kaplan, Ageliki G Vouyouka, Michael L Marin
OBJECTIVE: We have shown that vascular surgeon- hospitalist co management resulted in improved in-hospital mortality rates. We now aim to assess the impact of the hospitalist co management service (HCS) on healthcare cost. METHODS: A total of 1558 patients were divided into three cohorts and compared: 516 in 2012, 525 in 2013, and 517 in 2014. The HCS began in January 2013. Data were standardized for six vascular surgeons that were present 2012-2014. New attendings were excluded...
March 2017: Journal of Vascular Surgery
Xin-Sheng Deng, Xianzhong Meng, Rui Song, David Fullerton, James Jaggers
BACKGROUND: Calcific aortic valve disease (CAVD) is an age-related and slowly progressive valvular disorder. We have previously found that the increased inflammatory and osteogenic responses to Toll-like receptor 4 (TLR4) stimulation is correlated with lower signal transducer and activator of transcription 3 (Stat3) activity in aortic valve interstitial cells (AVICs). Rapamycin, a drug used clinically, induces feedback activation of Akt. Akt in turn may upregulate Stat3. Therefore we hypothesized that rapamycin will decrease TLR4-induced osteogenic response in human AVICs through modulation of Stat3 activity...
October 2016: Annals of Thoracic Surgery
Andrew K Capulli, Luke A MacQueen, Blakely B O'Connor, Stephanie Dauth, Kevin Kit Parker
Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease...
July 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Antonio Caracausi, Guillaume Avice, Peter G Burnard, Evelyn Füri, Bernard Marty
Noble gas isotopes are powerful tracers of the origins of planetary volatiles, and the accretion and evolution of the Earth. The compositions of magmatic gases provide insights into the evolution of the Earth's mantle and atmosphere. Despite recent analytical progress in the study of planetary materials and mantle-derived gases, the possible dual origin of the planetary gases in the mantle and the atmosphere remains unconstrained. Evidence relating to the relationship between the volatiles within our planet and the potential cosmochemical end-members is scarce...
May 5, 2016: Nature
Bok-Rye Lee, Rashed Zaman, Jean-Christophe Avice, Alain Ourry, Tae-Hwan Kim
To investigate the varietal difference in sulfur use efficiency (SUE) and drought stress tolerance, Brassica napus 'Mosa' and 'Saturnin' were exposed to polyethylene glycol (PEG)-induced drought stress for 72 h. Direct quantification of S uptake, de novo synthesis of amino acids and proteins was performed by tracing (34)S. The responses of photosynthetic activity in relation to SUE were also examined. The total amount of newly absorbed S decreased with drought stress in both cultivars but the decrease rate was significantly higher in Mosa (-64%) than in Saturnin (-41%)...
2016: Frontiers in Plant Science
Marine Poret, Balakumaran Chandrasekar, Renier A L van der Hoorn, Jean-Christophe Avice
Oilseed rape (Brassica napus L.) is a crop plant characterized by a poor nitrogen (N) use efficiency that is mainly due to low N remobilization efficiency during the sequential leaf senescence of the vegetative stage. As a high leaf N remobilization efficiency was strongly linked to a high remobilization of proteins during leaf senescence of rapeseed, our objective was to identify senescence-associated protease activities implicated in the protein degradation. To reach this goal, leaf senescence processes and protease activities were investigated in a mature leaf becoming senescent in plants subjected to ample or low nitrate supply...
May 2016: Plant Science: An International Journal of Experimental Plant Biology
Sophie Brunel-Muguet, Alain Mollier, François Kauffmann, Jean-Christophe Avice, Damien Goudier, Emmanuelle Sénécal, Philippe Etienne
Sulfur (S) nutrition in rapeseed (Brassica napus L.) is a major concern for this high S-demanding crop, especially in the context of soil S oligotrophy. Therefore, predicting plant growth, S plant allocation (between the plant's compartments) and S pool partitioning (repartition of the mobile-S vs. non-mobile-S fractions) until the onset of reproductive phase could help in the diagnosis of S deficiencies during the early stages. For this purpose, a process-based model, SuMoToRI (Sulfur Model Toward Rapeseed Improvement), was developed up to the onset of pod formation...
2015: Frontiers in Plant Science
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
Zhao-shun Yuan, Yang-zhao Zhou, Xiao-bo Liao, Jia-wen Luo, Kang-jun Shen, Ye-rong Hu, Lu Gu, Jian-ming Li, Chang-ming Tan, He-ming Chen, Xin-min Zhou
Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs...
December 2015: Amino Acids
Qingzhou Yao, Rui Song, Lihua Ao, Qiong Zhan, Joseph C Cleveland, Xiyong Yu, David A Fullerton, Xianzhong Meng
UNLABELLED: Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. While aortic valve interstitial cells (AVICs) are the main cells that express osteogenic mediators, the molecular mechanism that mediates AVIC osteogenic responses is incompletely understood. This study aims to identify pro-osteogenic factors in human AVICs affected by CAVD. METHODS AND RESULTS: Microarray analysis identified 11 up-regulated genes in AVICs of diseased valves...
September 2015: Biochimica et Biophysica Acta
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