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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28729366/recommendation-on-design-execution-and-reporting-of-animal-atherosclerosis-studies-a-scientific-statement-from-the-american-heart-association
#1
REVIEW
Alan Daugherty, Alan R Tall, Mat J A P Daemen, Erling Falk, Edward A Fisher, Guillermo García-Cardeña, Aldons J Lusis, A Phillip Owens, Michael E Rosenfeld, Renu Virmani
Animal studies are a foundation for defining mechanisms of atherosclerosis and potential targets of drugs to prevent lesion development or reverse the disease. In the current literature, it is common to see contradictions of outcomes in animal studies from different research groups, leading to the paucity of extrapolations of experimental findings into understanding the human disease. The purpose of this statement is to provide guidelines for development and execution of experimental design and interpretation in animal studies...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729365/induced-pluripotent-stem-cell-derived-endothelial-cells-in-insulin-resistance-and-metabolic-syndrome
#2
REVIEW
Ivan Carcamo-Orive, Ngan F Huang, Thomas Quertermous, Joshua W Knowles
Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729364/tgf-%C3%AE-transforming-growth-factor-%C3%AE-signaling-protects-the-thoracic-and-abdominal-aorta-from-angiotensin-ii-induced-pathology-by-distinct-mechanisms
#3
Stoyan N Angelov, Jie Hong Hu, Hao Wei, Nathan Airhart, Minghui Shi, David A Dichek
OBJECTIVE: The role of TGF-β (transforming growth factor-β) signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729363/brg1-brahma-related-gene-1-promotes-endothelial-mrtf-transcription-to-establish-embryonic-capillary-integrity
#4
Matthew T Menendez, E-Ching Ong, Brian T Shepherd, Vijay Muthukumar, Robert Silasi-Mansat, Florea Lupu, Courtney T Griffin
OBJECTIVE: The chromatin remodeling enzyme BRG1 (brahma-related gene 1) transcriptionally regulates target genes important for early blood vessel development and primitive hematopoiesis. However, because Brg1 deletion in vascular progenitor cells results in lethal anemia by embryonic day 10.5 (E10.5), roles for BRG1 in embryonic vascular development after midgestation are unknown. In this study, we sought to determine whether endothelial cell BRG1 regulates genes important for vascular development or maintenance later in embryonic development...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729362/sema3f-semaphorin-3f-selectively-drives-an-extraembryonic-proangiogenic-program
#5
Donatella Regano, Alessia Visintin, Fabiana Clapero, Federico Bussolino, Donatella Valdembri, Federica Maione, Guido Serini, Enrico Giraudo
OBJECTIVE: Molecular pathways governing blood vessel patterning are vital to vertebrate development. Because of their ability to counteract proangiogenic factors, antiangiogenic secreted Sema3 (class 3 semaphorins) control embryonic vascular morphogenesis. However, if and how Sema3 may play a role in the control of extraembryonic vascular development is presently unknown. APPROACH AND RESULTS: By characterizing genetically modified mice, here, we show that surprisingly Sema3F acts instead as a selective extraembryonic but not intraembryonic proangiogenic cue...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729361/cetp-cholesteryl-ester-transfer-protein-inhibition-with-anacetrapib-decreases-production-of-lipoprotein-a-in-mildly-hypercholesterolemic-subjects
#6
Tiffany Thomas, Haihong Zhou, Wahida Karmally, Rajasekhar Ramakrishnan, Stephen Holleran, Yang Liu, Patricia Jumes, John A Wagner, Brian Hubbard, Stephen F Previs, Thomas Roddy, Amy O Johnson-Levonas, David E Gutstein, Santica M Marcovina, Daniel J Rader, Henry N Ginsberg, John S Millar, Gissette Reyes-Soffer
OBJECTIVE: Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib. APPROACH AND RESULTS: We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28705796/tracking-adventitial-fibroblast-contribution-to-disease-a-review-of-current-methods-to-identify-resident-fibroblasts
#7
REVIEW
Jill T Kuwabara, Michelle D Tallquist
Cells present in the adventitia, or outermost layer of the blood vessel, contribute to the progression of vascular diseases, such as atherosclerosis, hypertension, and aortic dissection. The adventitial fibroblast of the aorta is the prototypic perivascular fibroblast, but the adventitia is composed of multiple distinct cell populations. Therefore, methods for uniquely identifying the fibroblast are critical for a better understanding of how these cells contribute to disease processes. A popular method for distinguishing adventitial cell types relies on the use of genetic tools in the mouse to trace and manipulate these cells...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28705795/selective-deletion-of-leptin-signaling-in-endothelial-cells-enhances-neointima-formation-and-phenocopies-the-vascular-effects-of-diet-induced-obesity-in-mice
#8
Astrid Hubert, Magdalena L Bochenek, Eva Schütz, Rajinikanth Gogiraju, Thomas Münzel, Katrin Schäfer
OBJECTIVE: Obesity is associated with elevated circulating leptin levels and hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on endothelial cells, and leptin promotes neointima formation in a receptor-dependent manner. Our aim was to examine the importance of endothelial LepR (End.LepR) signaling during vascular remodeling and to determine whether the cardiovascular consequences of obesity are because of hyperleptinemia or endothelial leptin resistance. APPROACH AND RESULTS: Mice with loxP-flanked LepR alleles were mated with mice expressing Cre recombinase controlled by the inducible endothelial receptor tyrosine kinase promoter...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28705794/targeted-disruption-of-jcad-junctional-protein-associated-with-coronary-artery-disease-kiaa1462-a-coronary-artery-disease-associated-gene-product-inhibits-angiogenic-processes-in-vitro-and-in-vivo
#9
Tetsuya Hara, Tomoko Monguchi, Noriko Iwamoto, Masaya Akashi, Kenta Mori, Toshihiko Oshita, Mitsumasa Okano, Ryuji Toh, Yasuhiro Irino, Masakazu Shinohara, Yui Yamashita, Go Shioi, Mikio Furuse, Tatsuro Ishida, Ken-Ichi Hirata
OBJECTIVE: Recent genome-wide association studies newly identified the human KIAA1462 gene as a new locus for coronary artery disease. However, the function of the gene product, named JCAD (junctional protein associated with coronary artery disease), is unknown. Because JCAD is expressed at cell-cell junctions in endothelial cells, we hypothesized and tested whether JCAD regulates angiogenic processes in vitro and in vivo. APPROACH AND RESULTS: Cell culture experiments revealed impaired angiogenic ability (proliferation, migration, and cord formation) by the knockdown of JCAD with siRNA (P<0...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28705793/dachsous1-fat4-signaling-controls-endothelial-cell-polarization-during-lymphatic-valve-morphogenesis
#10
Francoise Pujol, Tina Hodgson, Ines Martinez-Corral, Anne-Catherine Prats, Danelle Devenport, Masatoshi Takeichi, Elisabeth Genot, Taija Mäkinen, Philippa Francis-West, Barbara Garmy-Susini, Florence Tatin
OBJECTIVE: The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature. APPROACH AND RESULTS: Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1(high) cells) are disoriented and failed to form proper valve leaflets...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28705792/deletion-of-fstl1-follistatin-like-1-from-the-endocardial-endothelial-lineage-causes-mitral-valve-disease
#11
Stuti Prakash, Luis J J Borreguero, Marc Sylva, Lorena Flores Ruiz, Fereshte Rezai, Quinn D Gunst, José-Luis de la Pompa, Jan M Ruijter, Maurice J B van den Hoff
OBJECTIVE: Fstl1 (Follistatin-like 1) is a secreted protein that is expressed in the atrioventricular valves throughout embryonic development, postnatal maturation, and adulthood. In this study, we investigated the loss of Fstl1 in the endocardium/endothelium and their derived cells. APPROACH AND RESULTS: We conditionally ablated Fstl1 from the endocardial lineage using a transgenic Tie2-Cre mouse model. These mice showed a sustained Bmp and Tgfβ signaling after birth...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28684614/ubiquinol-effects-on-antiphospholipid-syndrome-prothrombotic-profile-a-randomized-placebo-controlled-trial
#12
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Abalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio Gonzalez-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10[Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28684613/endothelial-cell-autophagy-maintains-shear-stress-induced-nitric-oxide-generation-via-glycolysis-dependent-purinergic-signaling-to-endothelial-nitric-oxide-synthase
#13
Leena P Bharath, Jae Min Cho, Seul-Ki Park, Ting Ruan, Youyou Li, Robert Mueller, Tyler Bean, Van Reese, Russel S Richardson, Jinjin Cai, Ashot Sargsyan, Karla Pires, Pon Velayutham Anandh Babu, Sihem Boudina, Timothy E Graham, J David Symons
OBJECTIVE: Impaired endothelial cell (EC) autophagy compromises shear stress-induced nitric oxide (NO) generation. We determined the responsible mechanism. APPROACH AND RESULTS: On autophagy compromise in bovine aortic ECs exposed to shear stress, a decrease in glucose uptake and EC glycolysis attenuated ATP production. We hypothesized that decreased glycolysis-dependent purinergic signaling via P2Y1 (P2Y purinoceptor 1) receptors, secondary to impaired autophagy in ECs, prevents shear-induced phosphorylation of eNOS (endothelial nitric oxide synthase) at its positive regulatory site S1117 (p-eNOS(S1177)) and NO generation...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28684612/the-effect-of-iron-status-on-risk-of-coronary-artery-disease-a-mendelian-randomization-study
#14
Dipender Gill, Fabiola Del Greco M, Ann P Walker, Surjit K S Srai, Michael A Laffan, Cosetta Minelli
OBJECTIVE: Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). APPROACH AND RESULTS: A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663258/ly6c-high-monocytes-oscillate-in-the-heart-during-homeostasis-and-after-myocardial-infarction
#15
Maximilian J Schloss, Michael Hilby, Katrin Nitz, Raquel Guillamat Prats, Bartolo Ferraro, Giovanna Leoni, Oliver Soehnlein, Thorsten Kessler, Wenyan He, Bruno Luckow, Michael Horckmans, Christian Weber, Johan Duchene, Sabine Steffens
OBJECTIVE: Circadian regulation of neutrophil homeostasis affects myocardial infarction (MI) healing. It is unknown whether diurnal variations of monocyte counts exist in the heart and whether this affects their cardiac infiltration in response to MI. APPROACH AND RESULTS: Murine blood and organs were harvested at distinct times of day and analyzed by flow cytometry. Ly6C(high) monocyte surface expression levels of chemokine receptors (CCR) were ≈2-fold higher at the beginning of the active phase, Zeitgeber Time (ZT) 13 compared with ZT5...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663257/smooth-muscle-cells-derived-from-second-heart-field-and-cardiac-neural-crest-reside-in-spatially-distinct-domains-in-the-media-of-the-ascending-aorta
#16
Hisashi Sawada, Debra L Rateri, Jessica J Moorleghen, Mark W Majesky, Alan Daugherty
OBJECTIVE: Smooth muscle cells (SMCs) of the proximal thoracic aorta are embryonically derived from the second heart field (SHF) and cardiac neural crest (CNC). However, distributions of these embryonic origins are not fully defined. The regional distribution of SMCs of different origins is speculated to cause region-specific aortopathies. Therefore, the aim of this study was to determine the distribution of SMCs of SHF and CNC origins in the proximal thoracic aorta. APPROACH AND RESULTS: Mice with repressed LacZ in the ROSA26 locus were bred to those expressing Cre controlled by either the Wnt1 or Mef2c (myocyte-specific enhancer factor 2c) promoter to trace CNC- and SHF-derived SMCs, respectively...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663256/magnesium-counteracts-vascular-calcification-passive-interference-or-active-modulation
#17
REVIEW
Anique D Ter Braake, Catherine M Shanahan, Jeroen H F de Baaij
Over the last decade, an increasing number of studies report a close relationship between serum magnesium concentration and cardiovascular disease risk in the general population. In end-stage renal disease, an association was found between serum magnesium and survival. Hypomagnesemia was identified as a strong predictor for cardiovascular disease in these patients. A substantial body of in vitro and in vivo studies has identified a protective role for magnesium in vascular calcification. However, the precise mechanisms and its contribution to cardiovascular protection remain unclear...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663255/subcutaneous-adipocyte-lipolysis-contributes-to-circulating-lipid-levels
#18
Mikael Rydén, Peter Arner
OBJECTIVE: Fatty acids released via fat cell lipolysis can affect circulating lipid levels. However, the contribution of different lipolysis measures in adipose tissue is unknown and was presently examined in isolated subcutaneous adipocytes. APPROACH AND RESULTS: One thousand and sixty-six men and women were examined for lipolysis regulation in subcutaneous abdominal fat cells. Results were compared with fasting plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol (HDL-C) and triglycerides...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663254/blood-pressure-and-heart-rate-measures-associated-with-increased-risk-of-covert-brain-infarction-and-worsening-leukoaraiosis-in-older-adults
#19
Lester Y Leung, Traci M Bartz, Kenneth Rice, James Floyd, Bruce Psaty, Jose Gutierrez, W T Longstreth, Kenneth J Mukamal
OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings. APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis)...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28663253/inner-mitochondrial-membrane-disruption-links-apoptotic-and-agonist-initiated-phosphatidylserine-externalization-in-platelets
#20
Hyo-Jung Choo, Andaleb Kholmukhamedov, ChengZing Zhou, Shawn Jobe
OBJECTIVE: Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. APPROACH AND RESULTS: Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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