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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28619997/cardiotonic-steroids-stimulate-macrophage-inflammatory-responses-through-a-pathway-involving-cd36-tlr4-and-na-k-atpase
#1
Yiliang Chen, Wenxin Huang, Moua Yang, Gang Xin, Weiguo Cui, Zijian Xie, Roy L Silverstein
OBJECTIVE: Circulating levels of cardiotonic steroids (CTS) are elevated in various chronic inflammatory conditions, but the role of CTS in inflammation remains largely unknown. We have previously shown that the CTS ouabain stimulates proinflammatory responses in murine macrophages. In this study, we aim to explore the mechanism how CTS induce proinflammatory responses in primary murine and human macrophages. APPROACH AND RESULTS: Using both murine peritoneal macrophages and human monocyte-derived macrophages, we demonstrated that ouabain activated NF-κB, leading to proinflammatory cytokine (eg, MCP-1, tumor necrosis factor-α, interleukin-1β, and interleukin-6) production...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#2
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619995/codependence-of-bone-morphogenetic-protein-receptor-2-and-transforming-growth-factor-%C3%AE-in-elastic-fiber-assembly-and-its-perturbation-in-pulmonary-arterial-hypertension
#3
Nancy F Tojais, Aiqin Cao, Ying-Ju Lai, Lingli Wang, Pin-I Chen, Miguel A Alejandre Alcazar, Vinicio de Jesus Perez, Rachel K Hopper, Christopher J Rhodes, Matthew A Bill, Lynn Y Sakai, Marlene Rabinovitch
OBJECTIVE: We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether in addition to increased production of elastase by PA smooth muscle cells previously reported, PA elastic fibers are susceptible to degradation because of their abnormal assembly. APPROACH AND RESULTS: Fibrillin-1 and elastin are the major components of elastic fibers, and fibrillin-1 binds bone morphogenetic proteins (BMPs) and the large latent complex of transforming growth factor-β1 (TGFβ1)...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596377/trowaglerix-venom-polypeptides-as-a-novel-antithrombotic-agent-by-targeting-immunoglobulin-like-domains-of-glycoprotein-vi-in-platelet
#4
Chien-Hsin Chang, Ching-Hu Chung, Yi-Shu Tu, Cheng-Chieh Tsai, Chun-Chieh Hsu, Hui-Chin Peng, Yufeng J Tseng, Tur-Fu Huang
OBJECTIVE: Currently prescribed antiplatelet drugs have 1 common side effect-an increased risk of hemorrhage and thrombocytopenia. On the contrary, bleeding defects associated with glycoprotein VI (GPVI) expression deficiency are usually slightly prolonged bleeding times. However, GPVI antagonists are lacking in clinic. APPROACH AND RESULTS: Using reverse-phase high-performance liquid chromatography and sequencing, we revealed the partial sequence of trowaglerix α subunit, a potent specific GPVI-targeting snaclec (snake venom C-type lectin protein)...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596376/cre-lox-studies-identify-resident-macrophages-as-the-major-source-of-circulating-coagulation-factor-xiii-a
#5
Cora M L Beckers, Kingsley R Simpson, Kathryn J Griffin, Jane M Brown, Lih T Cheah, Kerrie A Smith, Jean Vacher, Paul A Cordell, Mark T Kearney, Peter J Grant, Richard J Pease
OBJECTIVE: To establish the cellular source of plasma factor (F)XIII-A. APPROACH AND RESULTS: A novel mouse floxed for the F13a1 gene, FXIII-A(flox/flox) (Flox), was crossed with myeloid- and platelet-cre-expressing mice, and cellular FXIII-A mRNA expression and plasma and platelet FXIII-A levels were measured. The platelet factor 4-cre.Flox cross abolished platelet FXIII-A and reduced plasma FXIII-A to 23±3% (P<0.001). However, the effect of platelet factor 4-cre on plasma FXIII-A was exerted outside of the megakaryocyte lineage because plasma FXIII-A was not reduced in the Mpl(-/-) mouse, despite marked thrombocytopenia...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596375/nlrp3-inflammasome-inhibition-by-mcc950-reduces-atherosclerotic-lesion-development-in-apolipoprotein-e-deficient-mice
#6
Thomas van der Heijden, Eva Kritikou, Wouter Venema, Janine van Duijn, Peter J van Santbrink, Bram Slütter, Amanda C Foks, Ilze Bot, Johan Kuiper
OBJECTIVE: Inflammasomes are multiprotein complexes, and their activation has been associated with cardiovascular disease. Inflammasome activation leads to secretion of caspase-1 by innate immune cells, resulting in the activation of interleukin-1β. Recently, a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, was described. In this study, we investigated the effect of MCC950 on atherosclerotic lesion development in apoE(-/-) mice. APPROACH AND RESULTS: First, we determined the efficacy of MCC950 in vitro...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596374/lrp1-dependent-bmper-signaling-regulates-lipopolysaccharide-induced-vascular-inflammation
#7
Pamela Lockyer, Hua Mao, Qiying Fan, Luge Li, Li-Yuan Yu-Lee, N Tony Eissa, Cam Patterson, Liang Xie, Xinchun Pi
OBJECTIVE: Bacterial endotoxin (lipopolysaccharide)-mediated sepsis involves dysregulated systemic inflammation, which injures the lung and other organs, often fatally. Vascular endothelial cells act as both targets and mediators of lipopolysaccharide-induced inflammatory responses. Dysfunction of endothelium results in increases of proinflammatory cytokine production and permeability leakage. BMPER (bone morphogenetic protein-binding endothelial regulator), an extracellular modulator of bone morphogenetic protein signaling, has been identified as a vital component in chronic endothelial inflammatory responses and atherosclerosis...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596373/mitochondrial-oxidative-stress-promotes-atherosclerosis-and-neutrophil-extracellular-traps-in-aged-mice
#8
Ying Wang, Wei Wang, Nan Wang, Alan R Tall, Ira Tabas
RATIONALE: Mitochondrial oxidative stress (mitoOS) has been shown to be increased in various cell types in human atherosclerosis and with aging. However, the role of cell type-specific mitoOS in atherosclerosis in the setting of advanced age and the molecular mechanisms remains to be determined in vivo. OBJECTIVE: The aim of this study was to examine the role of myeloid cell mitoOS in atherosclerosis in aged mice. APPROACH AND RESULTS: Lethally irradiated low-density lipoprotein receptor-deficient mice (Ldlr(-/-) ) were reconstituted with bone marrow from either wild-type or mitochondrial catalase (mCAT) mice...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28596372/human-blood-monocyte-subsets-a-new-gating-strategy-defined-using-cell-surface-markers-identified-by-mass-cytometry
#9
Graham D Thomas, Anouk A J Hamers, Catherine Nakao, Paola Marcovecchio, Angela M Taylor, Chantel McSkimming, Anh Tram Nguyen, Coleen A McNamara, Catherine C Hedrick
OBJECTIVE: Human monocyte subsets are defined as classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), and nonclassical (CD14(+)CD16(+)). Alterations in monocyte subset frequencies are associated with clinical outcomes, including cardiovascular disease, in which circulating intermediate monocytes independently predict cardiovascular events. However, delineating mechanisms of monocyte function is hampered by inconsistent results among studies. APPROACH AND RESULTS: We use cytometry by time-of-flight mass cytometry to profile human monocytes using a panel of 36 cell surface markers...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28572160/oxidized-phospholipids-and-risk-of-calcific-aortic-valve-disease-the-copenhagen-general-population-study
#10
Pia R Kamstrup, Ming-Yow Hung, Joseph L Witztum, Sotirios Tsimikas, Børge G Nordestgaard
OBJECTIVE: Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a). APPROACH AND RESULTS: A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease...
June 1, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28572159/apol1-risk-variants-and-cardiovascular-disease-results-from-the-aask-african-american-study-of-kidney-disease-and-hypertension
#11
Teresa K Chen, Lawrence J Appel, Morgan E Grams, Adrienne Tin, Michael J Choi, Michael S Lipkowitz, Cheryl A Winkler, Michelle M Estrella
OBJECTIVE: Among black, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS: In a cohort of blacks with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes...
June 1, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28572158/plasminogen-activator-inhibitor-1-is-a-marker-and-a-mediator-of-senescence
#12
Douglas E Vaughan, Rahul Rai, Sadiya S Khan, Mesut Eren, Asish K Ghosh
PAI-1 (plasminogen activator inhibitor-1) is a member of the evolutionarily conserved serine protease inhibitor family and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. Organismal homeostasis requires physiological levels of endogenous PAI-1, and increased PAI-1 production guides the onset and progression of numerous human diseases and contributes to the multimorbidity of aging. Both chronological and stress-induced accelerated aging are associated with cellular senescence and accompanied by marked increases in PAI-1 expression in tissues...
June 1, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28546220/activation-of-adiponectin-receptor-regulates-proprotein-convertase-subtilisin-kexin-type-9-expression-and-inhibits-lesions-in-apoe-deficient-mice
#13
Lei Sun, Xiaoxiao Yang, Qi Li, Peng Zeng, Ying Liu, Lipei Liu, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Yan Li, Rongxin Zhang, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
OBJECTIVE: The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28546219/inos-derived-nitric-oxide-induces-integrin-linked-kinase-endocytic-lysosome-mediated-degradation-in-the-vascular-endothelium
#14
Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Marquez, Rocio Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with inducible NO synthase knockout mice...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28546217/increased-hepatic-expression-of-endothelial-lipase-inhibits-cholesterol-diet-induced-hypercholesterolemia-and-atherosclerosis-in-transgenic-rabbits
#16
Chuan Wang, Kazutoshi Nishijima, Shuji Kitajima, Manabu Niimi, Haizhao Yan, Yajie Chen, Bo Ning, Fumikazu Matsuhisa, Enqi Liu, Jifeng Zhang, Y Eugene Chen, Jianglin Fan
OBJECTIVE: Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. APPROACH AND RESULTS: We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28522698/oligogalacturonic-acid-inhibits-vascular-calcification-by-two-mechanisms-inhibition-of-vascular-smooth-muscle-cell-osteogenic-conversion-and-interaction-with-collagen
#17
Ahmed Hodroge, Eric Trécherel, Marjorie Cornu, Walaa Darwiche, Ali Mansour, Katia Ait-Mohand, Thomas Verissimo, Cathy Gomila, Carole Schembri, Sophie Da Nascimento, Redouan Elboutachfaiti, Agnès Boullier, Emmanuel Lorne, Josiane Courtois, Emmanuel Petit, Sylvestre Toumieux, José Kovensky, Pascal Sonnet, Ziad A Massy, Saïd Kamel, Claire Rossi, Jérôme Ausseil
OBJECTIVE: Cardiovascular diseases constitute the leading cause of mortality worldwide. Calcification of the vessel wall is associated with cardiovascular morbidity and mortality in patients having many diseases, including diabetes mellitus, atherosclerosis, and chronic kidney disease. Vascular calcification is actively regulated by inductive and inhibitory mechanisms (including vascular smooth muscle cell adaptation) and results from an active osteogenic process. During the calcification process, extracellular vesicles (also known as matrix vesicles) released by vascular smooth muscle cells interact with type I collagen and then act as nucleating foci for calcium crystallization...
May 18, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28522697/circulating-microrna-125b-predicts-the-presence-and-progression-of-uremic-vascular-calcification
#18
Chia-Ter Chao, You-Pi Liu, Sheng-Fang Su, Hsiang-Yuan Yeh, Hsuan-Yu Chen, Pei-Jung Lee, Wan-Jiun Chen, Yee-Ming Lee, Jenq-Wen Huang, Chih-Kang Chiang, Kuan-Yu Hung, Huei-Wen Chen
OBJECTIVE: Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand. APPROACH AND RESULTS: We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium...
May 18, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28522696/apolipoprotein-a-i-mimetic-peptides-discordance-between-in-vitro-and-in-vivo-properties
#19
Michael Ditiatkovski, Jonatan Palsson, Jaye Chin-Dusting, Alan T Remaley, Dmitri Sviridov
OBJECTIVE: Apolipoprotein A-I (apoA-I) mimetic peptides have antiatherogenic properties of high-density lipoprotein in vitro and have been shown to inhibit atherosclerosis in vivo. It is unclear, however, if each in vitro antiatherogenic property of these peptides translates to a corresponding activity in vivo, and if so, which of these contributes most to reduce atherosclerosis. APPROACH AND RESULTS: The effect of 7 apoA-I mimetic peptides, which were developed to selectively reproduce a specific component of the antiatherogenic properties of apoA-I, on the development of atherosclerosis was investigated in apolipoprotein E-deficient mice fed a high-fat diet for 4 or 12 weeks...
May 18, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28495931/neutrophil-extracellular-traps-drive-endothelial-to-mesenchymal-transition
#20
Elmar Pieterse, Nils Rother, Marjolein Garsen, Julia Hofstra, Simon Satchell, Markus Hoffmann, Markus Loeven, Hanneke Knaapen, Olivier van der Heijden, Jo Berden, Luuk Hilbrands, Johan van der Vlag
OBJECTIVE: An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure of NETs to the endothelium in a variety of hematologic and autoimmune disorders, including lupus nephritis. This study aims to unravel the mechanisms through which NETs jeopardize vascular integrity. APPROACH AND RESULTS: Microvascular and macrovascular endothelial cells were exposed to NETs, and subsequent effects on endothelial integrity and function were determined in vitro and in vivo...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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