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Arteriosclerosis, Thrombosis, and Vascular Biology

journal
https://www.readbyqxmd.com/read/29122817/apo-a-i-apolipoprotein-a-i-vascular-gene-therapy-provides-durable-protection-against-atherosclerosis-in-hyperlipidemic-rabbits
#1
Bradley K Wacker, Nagadhara Dronadula, Lianxiang Bi, Alexis Stamatikos, David A Dichek
OBJECTIVE: Gene therapy that expresses apo A-I (apolipoprotein A-I) from vascular wall cells has promise for preventing and reversing atherosclerosis. Previously, we reported that transduction of carotid artery endothelial cells with a helper-dependent adenoviral (HDAd) vector expressing apo A-I reduced early (4 weeks) fatty streak development in fat-fed rabbits. Here, we tested whether the same HDAd could provide long-term protection against development of more complex lesions. APPROACH AND RESULTS: Fat-fed rabbits (n=25) underwent bilateral carotid artery gene transfer, with their left and right common carotids randomized to receive either a control vector (HDAdNull) or an apo A-I-expressing vector (HDAdApoAI)...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29122816/local-hemodynamic-forces-after-stenting-implications-on-restenosis-and-thrombosis
#2
REVIEW
Jaryl Ng, Christos V Bourantas, Ryo Torii, Hui Ying Ang, Erhan Tenekecioglu, Patrick W Serruys, Nicolas Foin
Local hemodynamic forces are well-known to modulate atherosclerotic evolution, which remains one of the largest cause of death worldwide. Percutaneous coronary interventions with stent implantation restores blood flow to the downstream myocardium and is only limited by stent failure caused by restenosis, stent thrombosis, or neoatherosclerosis. Cumulative evidence has shown that local hemodynamic forces affect restenosis and the platelet activation process, modulating the pathophysiological mechanisms that lead to stent failure...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29122815/evaluation-of-the-pleiotropic-effects-of-statins-a-reanalysis-of-the-randomized-trial-evidence-using-egger-regression
#3
Christopher Labos, James M Brophy, George Davey Smith, Allan D Sniderman, George Thanassoulis
OBJECTIVE: To reanalyze data from recent randomized trials of statins to assess whether the benefits and risks of statins are mediated primarily via their LDL-C (low-density lipoprotein cholesterol) lowering effects or via other mechanisms. APPROACH AND RESULTS: We adapted Egger regression, a technique frequently used in Mendelian randomization studies to detect genetic pleiotropy, to reanalyze the available randomized control trial data of statin therapy. For cardiovascular end points, each 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 0...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29122814/non-endoplasmic-reticulum-based-calr-calreticulin-can-coordinate-heterocellular-calcium-signaling-and-vascular-function
#4
Lauren A Biwer, Miranda E Good, Kwangseok Hong, Rahul K Patel, Neha Agrawal, Robin Looft-Wilson, Swapnil K Sonkusare, Brant E Isakson
OBJECTIVE: In resistance arteries, endothelial cell (EC) extensions can make contact with smooth muscle cells, forming myoendothelial junction at holes in the internal elastic lamina (HIEL). At these HIEL, calcium signaling is tightly regulated. Because Calr (calreticulin) can buffer ≈50% of endoplasmic reticulum calcium and is expressed throughout IEL holes in small arteries, the only place where myoendothelial junctions form, we investigated the effect of EC-specific Calr deletion on calcium signaling and vascular function...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097367/sex-chromosome-complement-defines-diffuse-versus-focal-angiotensin-ii-induced-aortic-pathology
#5
Yasir Alsiraj, Sean E Thatcher, Eric Blalock, Bradley Fleenor, Alan Daugherty, Lisa A Cassis
OBJECTIVE: Aortic pathologies exhibit sexual dimorphism, with aneurysms in both the thoracic and abdominal aorta (ie, abdominal aortic aneurysm [AAA]) exhibiting higher male prevalence. Women have lower prevalence of aneurysms, but when they occur, aneurysms progress rapidly. To define mechanisms for these sex differences, we determined the role of sex chromosome complement and testosterone on the location and progression of angiotensin II (AngII)-induced aortic pathologies. APPROACH AND RESULTS: We used transgenic male mice expressing Sry on an autosome to create Ldlr (low-density lipoprotein receptor)-deficient male mice with an XY or XX sex chromosome complement...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097366/quantitative-trait-locus-mapping-of-macrophage-cholesterol-metabolism-and-crispr-cas9-editing-implicate-an-acat1-truncation-as-a-causal-modifier-variant
#6
Qimin Hai, Brian Ritchey, Peggy Robinet, Alexander M Alzayed, Greg Brubaker, Jinying Zhang, Jonathan D Smith
OBJECTIVE: Cholesterol metabolism is a dynamic process involving intracellular trafficking, cholesterol esterification, and cholesterol ester hydrolysis. Our objective was to identify genes that regulate macrophage cholesterol metabolism. APPROACHES AND RESULTS: We performed quantitative trait loci mapping of free and esterified cholesterol levels and the ratio of esterified to free cholesterol in acetylated low-density lipoprotein-loaded bone marrow-derived macrophages from an AKR×DBA/2 strain intercross...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097365/refrigeration-induced-binding-of-von-willebrand-factor-facilitates-fast-clearance-of-refrigerated-platelets
#7
Wenchun Chen, Samuel A Druzak, Yingchun Wang, Cassandra D Josephson, Karin M Hoffmeister, Jerry Ware, Renhao Li
OBJECTIVE: Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared on transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed. APPROACH AND RESULTS: Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097364/nonfasting-triglycerides-low-density-lipoprotein-cholesterol-and-heart-failure-risk-two-cohort-studies-of-113-554-individuals
#8
Anette Varbo, Børge G Nordestgaard
OBJECTIVE: The prevalence of heart failure is increasing in the aging population, and heart failure is a disease with large morbidity and mortality. There is, therefore, a need for identifying modifiable risk factors for prevention. We tested the hypothesis that high concentrations of nonfasting triglycerides and low-density lipoprotein cholesterol are associated with higher risk of heart failure in the general population. APPROACH AND RESULTS: 103 860 individuals from the Copenhagen General Population Study and 9694 from the Copenhagen City Heart Study were included in 2 prospective observational association studies...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097363/interrogation-of-the-atherosclerosis-associated-sort1-sortilin-1-locus-with-primary-human-hepatocytes-induced-pluripotent-stem-cell-hepatocytes-and-locus-humanized-mice
#9
Xiao Wang, Avanthi Raghavan, Derek T Peters, Evanthia E Pashos, Daniel J Rader, Kiran Musunuru
OBJECTIVE: The noncoding single-nucleotide polymorphism rs12740374 has been hypothesized to be the causal variant responsible for liver-specific modulation of SORT1(sortilin 1) expression (ie, expression quantitative trait locus) and, by extension, the association of the SORT1 locus on human chromosome 1p13 with low-density lipoprotein cholesterol levels and coronary heart disease. The goals of this study were to compare 3 different hepatocyte models in demonstrating that the rs12740374 minor allele sequence is responsible for transcriptional activation of SORT1 expression...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29097362/elevated-plasma-factor-ixa-activity-in-premenopausal-women-on-hormonal-contraception
#10
Pansakorn Tanratana, Paul Ellery, Pamela Westmark, Alan E Mast, John P Sheehan
OBJECTIVE: Combined oral contraceptives induce a reversible hypercoagulable state with an enhanced risk of venous thromboembolism, but the underlying mechanism(s) remain unclear. Subjects on combined oral contraceptives also demonstrate a characteristic resistance to APC (activated protein C) in the thrombin generation assay. Here, we report the potential role of plasma factor IXa (FIXa) as a mechanism for hormone-induced systemic hypercoagulability. APPROACH AND RESULTS: A novel assay was used to determine FIXa activity in plasma samples from volunteer blood donors...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074590/deletion-of-at2-receptor-prevents-shp-1-induced-vegf-inhibition-and-improves-blood-flow-reperfusion-in-diabetic-ischemic-hindlimb
#11
Judith Paquin-Veillette, Farah Lizotte, Stéphanie Robillard, Raphaël Béland, Marc-André Breton, Andréanne Guay, Marc-Antoine Despatis, Pedro Geraldes
OBJECTIVE: Ischemia caused by narrowing of femoral artery is a major cause of peripheral arterial disease and morbidity affecting patients with diabetes mellitus. We have previously reported that the inhibition of the angiogenic response to VEGF (vascular endothelial growth factor) in diabetic mice was associated with the increased expression of SHP-1 (SH2 domain-containing phosphatase 1), a protein that can be activated by the AT2 (angiotensin II type 2) receptor. Deletion of AT2 receptor has been shown to promote angiogenesis within the ischemic muscle...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074589/abca1-derived-nascent-high-density-lipoprotein-apolipoprotein-ai-and-lipids-metabolically-segregate
#12
Bingqing Xu, Baiba K Gillard, Antonio M Gotto, Corina Rosales, Henry J Pownall
OBJECTIVE: Reverse cholesterol transport comprises cholesterol efflux from ABCA1-expressing macrophages to apolipoprotein (apo) AI, giving nascent high-density lipoprotein (nHDL), esterification of nHDL-free cholesterol (FC), selective hepatic extraction of HDL lipids, and hepatic conversion of HDL cholesterol to bile salts, which are excreted. We tested this model by identifying the fates of nHDL-[(3)H]FC, [(14)C] phospholipid (PL), and [(125)I]apo AI in serum in vitro and in vivo. APPROACH AND RESULTS: During in vitro incubation of human serum, nHDL-[(3)H]FC and [(14)C]PL rapidly transfer to HDL and low-density lipoproteins (t1/2=2-7 minutes), whereas nHDL-[(125)I]apo AI transfers solely to HDL (t1/2<10 minutes) and to the lipid-free form (t1/2>480 minutes)...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074588/glp-1-elicits-an-intrinsic-gut-liver-metabolic-signal-to-ameliorate-diet-induced-vldl-overproduction-and-insulin-resistance
#13
Rituraj Khound, Jennifer Taher, Chris Baker, Khosrow Adeli, Qiaozhu Su
OBJECTIVE: Perturbations in hepatic lipid and very-low-density lipoprotein (VLDL) metabolism are involved in the pathogenesis of obesity and hepatic insulin resistance. The objective of this study is to delineate the mechanism of subdiaphragmatic vagotomy in preventing obesity, hyperlipidemia, and insulin resistance. APPROACH AND RESULTS: By subjecting the complete subdiaphragmatic vagotomized mice to various nutritional conditions and investigating hepatic de novo lipogenesis pathway, we found that complete disruption of subdiaphragmatic vagal signaling resulted in a significant decrease of circulating VLDL-triglyceride compared with the mice obtained sham procedure...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074587/relationship-between-total-serum-bilirubin-levels-and-carotid-and-femoral-atherosclerosis-in-familial-dyslipidemia
#14
Antonio J Amor, Emilio Ortega, Verónica Perea, Montserrat Cofán, Aleix Sala-Vila, Isabel Nuñez, Rosa Gilabert, Emilio Ros
OBJECTIVE: Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group. APPROACH AND RESULTS: We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074586/impact-of-cd14-polymorphisms-on-anti-apo-a-1-apolipoprotein-a-1-igg-related-coronary-artery-disease-prediction-in-the-general-population
#15
Panagiotis Antiochos, Pedro Marques-Vidal, Julien Virzi, Sabrina Pagano, Nathalie Satta, Oliver Hartley, Fabrizio Montecucco, François Mach, Zoltan Kutalik, Gerard Waeber, Peter Vollenweider, Nicolas Vuilleumier
OBJECTIVE: We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism. APPROACH AND RESULTS: In a prospectively studied, population-based cohort of 5220 subjects (mean age 52...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29074585/%C3%AE-5-fatty-acid-desaturase-fads1-impacts-metabolic-disease-by-balancing-proinflammatory-and-proresolving-lipid-mediators
#16
Anthony D Gromovsky, Rebecca C Schugar, Amanda L Brown, Robert N Helsley, Amy C Burrows, Daniel Ferguson, Renliang Zhang, Brian E Sansbury, Richard G Lee, Richard E Morton, Daniela S Allende, John S Parks, Matthew Spite, J Mark Brown
OBJECTIVE: Human genetic variants near the FADS (fatty acid desaturase) gene cluster (FADS1-2-3) are strongly associated with cardiometabolic traits including dyslipidemia, fatty liver, type 2 diabetes mellitus, and coronary artery disease. However, mechanisms underlying these genetic associations are unclear. APPROACH AND RESULTS: Here, we specifically investigated the physiological role of the Δ-5 desaturase FADS1 in regulating diet-induced cardiometabolic phenotypes by treating hyperlipidemic LDLR (low-density lipoprotein receptor)-null mice with antisense oligonucleotides targeting the selective knockdown of Fads1...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29051141/coronary-artery-ectasia-predicts-future-cardiac-events-in-patients-with-acute-myocardial-infarction
#17
Takahito Doi, Yu Kataoka, Teruo Noguchi, Tatsuhiro Shibata, Takahiro Nakashima, Shoji Kawakami, Kazuhiro Nakao, Masashi Fujino, Toshiyuki Nagai, Tomoaki Kanaya, Yoshio Tahara, Yasuhide Asaumi, Etsuko Tsuda, Michikazu Nakai, Kunihiro Nishimura, Toshihisa Anzai, Kengo Kusano, Hiroaki Shimokawa, Yoichi Goto, Satoshi Yasuda
OBJECTIVE: Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. APPROACH AND RESULTS: We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29051140/fgd5-faciogenital-dysplasia-5-regulates-vegf-vascular-endothelial-growth-factor-a-receptor-2-coupling-to-pi3-phosphoinositide-3-kinase-and-receptor-recycling
#18
Maikel A Farhan, Abul K Azad, Nicolas Touret, Allan G Murray
OBJECTIVE: VEGF (vascular endothelial growth factor-A) signaling to the endothelial cell (EC) through VEGFR2 (VEGF receptor-2) is the principal cue driving new blood vessel formation. FGD5 (faciogenital dysplasia-5)-a Rho-family guanine nucleotide exchange factor-is selectively expressed in EC. Deficiency of FGD5 is embryonically lethal in mice and perturbs angiogenesis and VEGF signal transduction. However, the mechanism of FGD5 regulation of VEGF signaling is poorly understood. APPROACH AND RESULTS: Angiogenic sprouting and EC cytoskeletal remodeling were evaluated in a 3-dimensional (3D) in vitro model...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29051139/mining-the-stiffness-sensitive-transcriptome-in-human-vascular-smooth-muscle-cells-identifies-long-noncoding-rna-stiffness-regulators
#19
Christopher Yu, Tina Xu, Richard Assoian, Daniel J Rader
OBJECTIVE: Vascular extracellular matrix stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic and coronary vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long noncoding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive (SS) transcriptome of human aortic and coronary VSMCs and identifies potential key lncRNA regulators of stiffness-dependent VSMC functions...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29025710/opposing-actions-of-akt-protein-kinase-b-isoforms-in-vascular-smooth-muscle-injury-and-therapeutic-response
#20
Yu Jin, Yi Xie, Allison C Ostriker, Xinbo Zhang, Renjing Liu, Monica Y Lee, Kristen L Leslie, Waiho Tang, Jing Du, Seung Hee Lee, Yingdi Wang, William C Sessa, John Hwa, Jun Yu, Kathleen A Martin
OBJECTIVE: Drug-eluting stent delivery of mTORC1 (mammalian target of rapamycin complex 1) inhibitors is highly effective in preventing intimal hyperplasia after coronary revascularization, but adverse effects limit their use for systemic vascular disease. Understanding the mechanism of action may lead to new treatment strategies. We have shown that rapamycin promotes vascular smooth muscle cell differentiation in an AKT2-dependent manner in vitro. Here, we investigate the roles of AKT (protein kinase B) isoforms in intimal hyperplasia...
October 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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