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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28183703/aup1-ancient-ubiquitous-protein-1-is-a-key-determinant-of-hepatic-very-low-density-lipoprotein-assembly-and-secretion
#1
Jing Zhang, Mostafa Zamani, Christoph Thiele, Jennifer Taher, Mohsen Amir Alipour, Zemin Yao, Khosrow Adeli
OBJECTIVE: AUP1 (ancient ubiquitous protein 1) is an endoplasmic reticulum-associated protein that also localizes to the surface of lipid droplets (LDs), with dual role in protein quality control and LD regulation. Here, we investigated the role of AUP1 in hepatic lipid mobilization and demonstrate critical roles in intracellular biogenesis of apoB100 (apolipoprotein B-100), LD mobilization, and very-low-density lipoprotein (VLDL) assembly and secretion. APPROACH AND RESULTS: siRNA knockdown of AUP1 significantly increased secretion of VLDL-sized apoB100-containing particles from HepG2 cells, correcting a key metabolic defect in these cells that normally do not secrete much VLDL...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28183702/glycated-hemoglobin-is-associated-with-the-growth-rate-of-abdominal-aortic-aneurysms-a-substudy-from-the-viva-viborg-vascular-randomized-screening-trial
#2
Katrine Lawaetz Kristensen, Marie Dahl, Lars Melholt Rasmussen, Jes Sanddal Lindholt
OBJECTIVE: An inverse association between abdominal aortic aneurysms (AAAs) and diabetes mellitus exists; however, the cause remains unknown. This study aimed to evaluate whether the degree of glycemia is associated with aneurysm growth. APPROACH AND RESULTS: The study was based on VIVA trial (Viborg Vascular), the randomized clinically controlled screening trial for abdominal aortic aneurysm in men aged 65 to 74 years in the Central Denmark Region. The screening included measurement of the abdominal aorta by ultrasound, analysis of glycated hemoglobin (HbA1c), and follow-up for ≤5 years for aneurysms <5 cm...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28183701/association-of-serum-hmgb2-levels-with-in-stent-restenosis-hmgb2-promotes-neointimal-hyperplasia-in-mice-with-femoral-artery-injury-and-proliferation-and-migration-of-vsmcs
#3
Yu Hu He, Xiao Qun Wang, Jian Zhang, Zhu Hui Liu, Wen Qi Pan, Ying Shen, Zheng Bin Zhu, Ling Jie Wang, Xiao Xiang Yan, Ke Yang, Rui Yan Zhang, Wei Feng Shen, Feng Hua Ding, Lin Lu
OBJECTIVE: In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in CAD patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. APPROACH AND RESULTS: From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28183700/2016-atvb-plenary-lecture-receptor-for-advanced-glycation-endproducts-and-implications-for-the-pathogenesis-an-treatment-of-cardiometabolic-disorders-spotlight-on-the-macrophage
#4
REVIEW
Ann Marie Schmidt
The receptor for advanced glycation endproducts (RAGE) interacts with a unique repertoire of ligands that form and collect in the tissues and circulation in diabetes mellitus, aging, inflammation, renal failure, and obesity. RAGE is expressed on multiple cell types linked to tissue perturbation in these settings. This brief review focuses on the role of RAGE in monocytes/macrophages and how RAGE ligand engagement on these cells mediates seminal changes in monocyte/macrophage migration, oxidative stress, cholesterol efflux, and pro- versus anti-inflammatory cues that signal to tissue damage...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153882/activated-platelets-induce-endothelial-cell-activation-via-an-interleukin-1%C3%AE-pathway-in-systemic-lupus-erythematosus
#5
Sokha Nhek, Robert Clancy, Kristen A Lee, Nicole M Allen, Tessa J Barrett, Emanuela Marcantoni, Janet Nwaukoni, Sara Rasmussen, Maya Rubin, Jonathan D Newman, Jill P Buyon, Jeffrey S Berger
OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. APPROACH AND RESULTS: Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153881/prevention-of-diet-induced-metabolic-dysregulation-inflammation-and-atherosclerosis-in-ldlr-mice-by-treatment-with-the-atp-citrate-lyase-inhibitor-bempedoic-acid
#6
Joshua P Samsoondar, Amy C Burke, Brian G Sutherland, Dawn E Telford, Cynthia G Sawyez, Jane Y Edwards, Stephen L Pinkosky, Roger S Newton, Murray W Huff
OBJECTIVE: Bempedoic acid (ETC-1002, 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel low-density lipoprotein cholesterol-lowering compound. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153880/tamoxifen-directly-inhibits-platelet-angiogenic-potential-and-platelet-mediated-metastasis
#7
Kelly E Johnson, Jodi A Forward, Mason D Tippy, Julia R Ceglowski, Saleh El-Husayni, Rajesh Kulenthirarajan, Kellie R Machlus, Erica L Mayer, Joseph E Italiano, Elisabeth M Battinelli
OBJECTIVE: Platelets, which are mainly known for their role in hemostasis, are now known to play a crucial role in metastasis. Tamoxifen is a selective estrogen receptor modulator that is widely used for the treatment of breast cancer. Tamoxifen and its metabolites have been shown to directly impact platelet function, suggesting that this drug has additional mechanisms of action. The purpose of this study was to determine whether tamoxifen exerts antitumor effects through direct platelet inhibition...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153879/angiogenic-factor-with-g-patch-and-fha-domains-1-is-a-novel-regulator-of-vascular-injury
#8
Bisheng Zhou, Sheng Zeng, Nan Li, Liming Yu, Guang Yang, Yuyu Yang, Xinjian Zhang, Mingming Fang, Jun Xia, Yong Xu
OBJECTIVE: Phenotypic modulation of vascular smooth muscle cells represents a hallmark event in vascular injury. The underlying mechanism is not completely sorted out. We investigated the involvement of angiogenic factor with G patch and FHA domains 1 (Aggf1) in vascular injury focusing on the transcriptional regulation of vascular smooth muscle cell signature genes. APPROACH AND RESULTS: We report here that Aggf1 expression was downregulated in several different cell models of phenotypic modulation in vitro and in the vessels after carotid artery ligation in mice...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153878/nlrp3-nucleotide-oligomerization-domain-like-receptor-family-pyrin-domain-containing-3-caspase-1-inflammasome-degrades-contractile-proteins-implications-for-aortic-biomechanical-dysfunction-and-aneurysm-and-dissection-formation
#9
Darrell Wu, Pingping Ren, Yanqiu Zheng, Lin Zhang, Gaiping Xu, Wanmu Xie, Eric E Lloyd, Sui Zhang, Qianzi Zhang, John A Curci, Joseph S Coselli, Dianna M Milewicz, Ying H Shen, Scott A LeMaire
OBJECTIVE: Increasing evidence suggests that contractile dysfunction in smooth muscle cells (SMCs) plays a critical role in aortic biomechanical dysfunction and aortic aneurysm and dissection (AAD) development. However, the mechanisms underlying SMC contractile dysfunction in sporadic AAD are poorly understood. In this study, we examined the role of the NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3)-caspase-1 inflammasome, a key inflammatory cascade, in SMC contractile dysfunction in AAD...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153877/recipients-of-the-2017-early-career-investigator-awards
#10
Alan Daugherty
No abstract text is available yet for this article.
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153876/biomarkers-of-calcific-aortic-valve-disease
#11
REVIEW
Aeron Small, Daniel Kiss, Jay Giri, Saif Anwaruddin, Hasan Siddiqi, Marie Guerraty, Julio A Chirinos, Giovanni Ferrari, Daniel J Rader
Calcific aortic valve disease (CAVD) is a highly prevalent cardiovascular disorder accounting for a rising economic and social burden on aging populations. In spite of continuing study on the pathophysiology of disease, there remain no medical therapies to prevent the progression of CAVD. The discovery of biomarkers represents a potentially complementary approach in stratifying risk and timing of intervention in CAVD and has the advantage of providing insight into causal factors for the disease. Biomarkers have been studied extensively in atherosclerotic cardiovascular disease, with success as additive for clinical and scientific purposes...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28153875/prognostic-impacts-of-plasma-levels-of-cyclophilin-a-in-patients-with-coronary-artery-disease
#12
Tomohiro Ohtsuki, Kimio Satoh, Junichi Omura, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Shinichiro Sunamura, Nobuhiro Yaoita, Tatsuo Aoki, Shunsuke Tatebe, Koichiro Sugimura, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
OBJECTIVE: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, and activated platelets in response to oxidative stress. We have recently demonstrated that plasma CyPA level is a novel biomarker for diagnosing coronary artery disease. However, it remains to be elucidated whether plasma CyPA levels also have a prognostic impact in such patients. APPROACH AND RESULTS: In 511 consecutive patients undergoing diagnostic coronary angiography, we measured the plasma levels of CyPA, high-sensitivity C-reactive protein (hsCRP), and brain natriuretic peptide and evaluated their prognostic impacts during the follow-up (42 months, interquartile range: 25-55 months)...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28126828/cetp-pharmacogenomics-based-response-to-the-cetp-inhibitor-dalcetrapib
#13
Jean-Claude Tardif, David Rhainds, Eric Rhéaume, Marie-Pierre Dubé
High-density lipoproteins are involved in reverse cholesterol transport and possess anti-inflammatory and antioxidative properties. Paradoxically, CETP inhibitors have been shown to increase inflammation as revealed by a raised plasma level of high-sensitivity C-reactive protein. CETP inhibitors did not improve clinical outcomes in large-scale clinical trials of unselected patients with coronary disease. Dalcetrapib is a CETP modulator in which effects on cardiovascular outcomes were demonstrated in the dal-OUTCOMES trial to be influenced by correlated polymorphisms in the ADCY9 (adenylate cyclase 9) gene (P=2...
January 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28126827/involvement-of-cetp-cholesteryl-ester-transfer-protein-in-the-shift-of-sphingosine-1-phosphate-among-lipoproteins-and-in-the-modulation-of-its-functions
#14
Makoto Kurano, Masumi Hara, Hitoshi Ikeda, Kazuhisa Tsukamoto, Yutaka Yatomi
OBJECTIVE: Sphingosine-1-phosphate (S1P) is a vasoprotective lipid mediator. About two thirds of plasma S1P rides on high-density lipoprotein (HDL), and several pleiotropic properties of HDL have been ascribed to S1P. In human subjects, CETP (cholesteryl ester transfer protein) greatly influences HDL quantities. In this study, we attempted to elucidate the roles of CETP in the metabolism of S1P. APPROACH AND RESULTS: We overexpressed CETP in mice that lacked CETP and found that CETP overexpression decreased the HDL level but failed to modulate the levels of S1P and apolipoprotein M (apoM), a carrier of S1P, in the total plasma...
January 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28126826/role-of-insulin-stimulated-adipose-tissue-perfusion-in-the-development-of-whole-body-insulin-resistance
#15
REVIEW
Anna L Emanuel, Rick I Meijer, Marcel H A Muskiet, Daniel H van Raalte, Etto C Eringa, Erik H Serné
After food ingestion, macronutrients are transported to and stored in the skeletal muscle and adipose tissue. They can be subsequently used as an energy source in times of energy deprivation. Uptake of these nutrients in myocytes and adipocytes depends largely on adequate tissue perfusion. Interestingly, insulin is able to dilate skeletal muscle arterioles, which facilitates the delivery of nutrients and insulin itself to muscle tissue. Insulin-stimulated skeletal muscle perfusion is impaired in several insulin-resistant states and is believed to contribute to impaired skeletal muscle and consequently whole-body glucose uptake...
January 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28126825/endosialin-promotes-atherosclerosis-through-phenotypic-remodeling-of-vascular-smooth-muscle-cells
#16
Zulfiyya Hasanov, Tina Ruckdeschel, Courtney König, Carolin Mogler, Stephanie S Kapel, Claudia Korn, Carleen Spegg, Viktoria Eichwald, Matthias Wieland, Sila Appak, Hellmut G Augustin
OBJECTIVE: Vascular smooth muscle cells (VSMC) play a key role in the pathogenesis of atherosclerosis, the globally leading cause of death. The transmembrane orphan receptor endosialin (CD248) has been characterized as an activation marker of cells of the mesenchymal lineage including tumor-associated pericytes, stromal myofibroblasts, and activated VSMC. We, therefore, hypothesized that VSMC-expressed endosialin may display functional involvement in the pathogenesis of atherosclerosis...
January 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#17
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082260/mechanisms-of-mas1-receptor-mediated-signaling-in-the-vascular-endothelium
#18
Brian R Hoffmann, Timothy J Stodola, Jordan R Wagner, Daniela N Didier, Eric C Exner, Julian H Lombard, Andrew S Greene
OBJECTIVE: Angiotensin II (AngII) has been shown to regulate angiogenesis and at high pathophysiological doses to cause vasoconstriction through the AngII receptor type 1. Angiotensin 1 to 7 (Ang-(1-7)) acting through the Mas1 receptor can act antagonistically to high pathophysiological levels of AngII by inducing vasodilation, whereas the effects of Ang-(1-7) signaling on angiogenesis are less defined. To complicate the matter, there is growing evidence that a subpressor dose of AngII produces phenotypes similar to Ang-(1-7)...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082259/identification-of-genetic-variants-linking-protein-c-and-lipoprotein-metabolism-the-aric-study-atherosclerosis-risk-in-communities
#19
James S Pankow, Weihong Tang, Nathan Pankratz, Weihua Guan, Lu-Chen Weng, Mary Cushman, Eric Boerwinkle, Aarossn R Folsom
OBJECTIVE: Previous studies have identified common genetic variants in 4 chromosomal regions that together account for 14% to 15% of the variance in circulating levels of protein C. To further characterize the genetic architecture of protein C, we obtained denser coverage at some loci, extended investigation of protein C to low-frequency and rare variants, and searched for new associations in genes known to influence protein C. APPROACH AND RESULTS: Genetic associations with protein C antigen level were evaluated in ≤10 778 European and 3190 black participants aged 45 to 64 years...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28082258/eepd1-is-a-novel-lxr-target-gene-in-macrophages-which-regulates-abca1-abundance-and-cholesterol-efflux
#20
Jessica Kristine Nelson, Duco Steven Koenis, Saskia Scheij, Emma Clare Laura Cook, Martina Moeton, Ana Santos, Jean-Marc Lobaccaro, Silvere Baron, Noam Zelcer
OBJECTIVE: The sterol-responsive nuclear receptors, liver X receptors α (LXRα, NR1H3) and β (LXRβ, NR1H2), are key determinants of cellular cholesterol homeostasis. LXRs are activated under conditions of high cellular sterol load and induce expression of the cholesterol efflux transporters ABCA1 and ABCG1 to promote efflux of excess cellular cholesterol. However, the full set of genes that contribute to LXR-stimulated cholesterol efflux is unknown, and their identification is the objective of this study...
January 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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