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Arteriosclerosis, Thrombosis, and Vascular Biology

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https://www.readbyqxmd.com/read/28798142/accumulation-of-smooth-muscle-22%C3%AE-protein-accelerates-senescence-of-vascular-smooth-muscle-cells-via-stabilization-of-p53-in-vitro-and-in-vivo
#1
Sui-Bing Miao, Xiao-Li Xie, Ya-Juan Yin, Li-Li Zhao, Fan Zhang, Ya-Nan Shu, Rong Chen, Peng Chen, Li-Hua Dong, Yan-Ling Lin, Pin Lv, Dan-Dan Zhang, Xi Nie, Zhen-Ying Xue, Mei Han
OBJECTIVE: Smooth muscle (SM) 22α, an actin-binding protein, displays an upregulated expression as a marker during cellular senescence. However, the causal relationship between SM22α and senescence is poorly understood. This study aimed to investigate the role of SM22α in angiotensin II (Ang II)-induced senescence of vascular smooth muscle cells (VSMCs). APPROACH AND RESULTS: We prepared a model of VSMC senescence induced by Ang II and found that the expression of SM22α in VSMCs was increased in response to chronic Ang II treatment...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28798141/characterization-of-macrophage-polarization-states-using-combined-measurement-of-2-deoxyglucose-and-glutamine-accumulation-implications-for-imaging-of-atherosclerosis
#2
Sina Tavakoli, Kevin Downs, John D Short, Huynh Nga Nguyen, Yanlai Lai, Paul A Jerabek, Beth Goins, Jakub Toczek, Mehran M Sadeghi, Reto Asmis
OBJECTIVE: Despite the early promising results of (18)F-fluorodeoxyglucose positron emission tomography for assessment of vessel wall inflammation, its accuracy in prospective identification of vulnerable plaques has remained limited. Additionally, previous studies have indicated that (18)F-fluorodeoxyglucose uptake alone may not allow for accurate identification of specific macrophage activation states. We aimed to determine whether combined measurement of glucose and glutamine accumulation-the 2 most important bioenergetic substrates for macrophages-improves the distinction of macrophage inflammatory states and can be utilized to image atherosclerosis...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28798140/the-hemoglobin-homolog-cytoglobin-in-smooth-muscle-inhibits-apoptosis-and-regulates-vascular-remodeling
#3
Frances L Jourd'heuil, Haiyan Xu, Timothy Reilly, Keneta McKellar, Chaymae El Alaoui, Julia Steppich, Yong Feng Liu, Wen Zhao, Roman Ginnan, David Conti, Reynold Lopez-Soler, Arif Asif, Rebecca K Keller, John J Schwarz, Le Thi Thanh Thuy, Norifumi Kawada, Xiaochun Long, Harold A Singer, David Jourd'heuil
OBJECTIVE: The role of hemoglobin and myoglobin in the cardiovascular system is well established, yet other globins in this context are poorly characterized. Here, we examined the expression and function of cytoglobin (CYGB) during vascular injury. APPROACH AND RESULTS: We characterized CYGB content in intact vessels and primary vascular smooth muscle (VSM) cells and used 2 different vascular injury models to examine the functional significance of CYGB in vivo. We found that CYGB was strongly expressed in medial arterial VSM and human veins...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28798139/impact-of-non-vitamin-k-antagonist-oral-anticoagulants-from-a-basic-science-perspective
#4
REVIEW
Maureane Hoffman, Dougald M Monroe
The biochemical properties of the non-vitamin K antagonist oral anticoagulants (NOACs) and their differences from the mechanism of action of vitamin K antagonists contribute to their properties as anticoagulants. These properties include as follows: (1) Inhibiting a single protease is much less effective at inhibiting coagulation than is inhibiting at multiple steps. Thus, the dose-response relationship between NOAC level and intensity of anticoagulation is shallower and more linear than that of vitamin K antagonists...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28775076/the-involvement-of-mirna-in-carotid-related-stroke
#5
REVIEW
Pierre Maitrias, Valérie Metzinger-Le Meuth, Joseph Nader, Thierry Reix, Thierry Caus, Laurent Metzinger
Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Stroke is associated with a marked disability burden and has a major economic impact; this is especially true for carotid artery stroke. Major advances in primary and secondary prevention during the last few decades have helped to tackle this public health problem. However, better knowledge of the physiopathology of stroke and its underlying genetic mechanisms is needed to improve diagnosis and therapy. miRNAs are an important, recently identified class of post-transcriptional regulators of gene expression and are known to be involved in cerebrovascular disease...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28775075/first-selective-12-lox-inhibitor-ml355-impairs-thrombus-formation-and-vessel-occlusion-in-vivo-with-minimal-effects-on-hemostasis
#6
Reheman Adili, Benjamin E Tourdot, Katherine Mast, Jennifer Yeung, John Cody Freedman, Abigail Green, Diane K Luci, Ajit Jadhav, Anton Simeonov, David J Maloney, Theodore R Holman, Michael Holinstat
OBJECTIVE: Adequate platelet reactivity is required for maintaining hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi. Platelet 12(S)-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated to regulate platelet function and thrombosis ex vivo, supporting a key role for 12-LOX in the regulation of in vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28775074/stasis-promotes-erythrocyte-adhesion-to-von-willebrand-factor
#7
Michel W J Smeets, Marjon J Mourik, Hans W M Niessen, Peter L Hordijk
OBJECTIVE: Venous thromboembolism is a major contributor to global disease burden. Leukocytes and platelets initiate thrombogenesis on blood stasis and initiate the formation of a fibrin, VWF (von Willebrand factor), and neutrophil extracellular trap scaffolds for erythrocytes. However, there is little knowledge on how erythrocytes become stably incorporated into this scaffold. Recently, we described the adhesion of calcium-loaded erythrocytes to endothelial-derived VWF strings. Because VWF is part of the scaffold of venous thrombi, we questioned whether reduced flow or stasis promotes the adhesion of normal erythrocytes to VWF and whether venous thrombi show evidence of erythrocyte-VWF interactions...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28775073/clots-are-potent-triggers-of-inflammatory-cell-gene-expression-indications-for-timely-fibrinolysis
#8
Robert A Campbell, Adriana Vieira-de-Abreu, Jesse W Rowley, Zechariah G Franks, Bhanu Kanth Manne, Matthew T Rondina, Larry W Kraiss, Jennifer J Majersik, Guy A Zimmerman, Andrew S Weyrich
OBJECTIVE: Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. Determine whether clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases. APPROACH AND RESULTS: We performed next-generation RNA sequencing on monocytes extracted from whole blood clots and using a purified plasma clot system...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28775072/lmo2-lim-domain-only-2-modulates-sphk1-sphingosine-kinase-and-promotes-endothelial-cell-migration
#9
Gianfranco Matrone, Shu Meng, Qilin Gu, Jie Lv, Longhou Fang, Kaifu Chen, John P Cooke
OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) (y1) zebra fish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751575/effects-of-intranasal-insulin-on-triglyceride-rich-lipoprotein-particle-production-in-healthy-men
#10
Changting Xiao, Satya Dash, Priska Stahel, Gary F Lewis
OBJECTIVE: Insulin administered directly into the brain acutely suppresses hepatic glucose production and triglyceride-rich lipoprotein (TRL) secretion in rodents. In addition, intranasally administered insulin, which selectively raises CSF insulin concentration, suppresses hepatic glucose production in humans; however, its effect on TRL secretion in humans has not previously been examined. In this study, we examined whether intranasal insulin, administered at a dose that has previously been shown to suppress hepatic glucose production, modulates TRL particle secretion by the liver and intestine in humans...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751574/expression-of-adamts13-in-normal-and-abnormal-placentae-and-its-potential-role-in-angiogenesis-and-placenta-development
#11
Juan Xiao, Yun Feng, Xueyin Li, Wei Li, Lei Fan, Jing Liu, Xue Zeng, Kaiyue Chen, Xi Chen, Xiaoshui Zhou, X Long Zheng, Suhua Chen
OBJECTIVE: ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis and its physiological role in placenta are not known. APPROACH AND RESULTS: We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751573/sox10-cells-contribute-to-vascular-development-in-multiple-organs
#12
Dong Wang, Fan Wu, Haoyong Yuan, Aijun Wang, Gyeong Jin Kang, Tan Truong, Lu Chen, Andrew S McCallion, Xiaohua Gong, Song Li
OBJECTIVE: Previous genetic lineage tracing studies showed that Sox10+ cells differentiate into vascular mural cells, limited to neural crest-derived blood vessels in craniofacial tissues, aortic arch, pulmonary arch arteries, brachiocephalic, carotid arteries, and thymus. The purpose of this study was to investigate the contribution of Sox10+ cells to the vascular development in other tissues and organs and their relationship with neural crest. APPROACH AND RESULTS: Using genetic lineage tracing technique based on Cre/LoxP system, we examined blood vessels of the adult organs of Sox10-Cre/Rosa-LoxP-red fluorescent protein and Wnt1-Cre/Rosa-LoxP-red fluorescent protein mice by immunohistological analysis...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751572/short-term-exposure-to-ambient-air-pollution-and-biomarkers-of-systemic-inflammation-the-framingham-heart-study
#13
Wenyuan Li, Kirsten S Dorans, Elissa H Wilker, Mary B Rice, Petter L Ljungman, Joel D Schwartz, Brent A Coull, Petros Koutrakis, Diane R Gold, John F Keaney, Ramachandran S Vasan, Emelia J Benjamin, Murray A Mittleman
OBJECTIVE: The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. APPROACH AND RESULTS: We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751571/in-vivo-base-editing-of-pcsk9-proprotein-convertase-subtilisin-kexin-type-9-as-a-therapeutic-alternative-to-genome-editing
#14
Alexandra C Chadwick, Xiao Wang, Kiran Musunuru
OBJECTIVE: High-efficiency genome editing to disrupt therapeutic target genes, such as PCSK9 (proprotein convertase subtilisin/kexin type 9), has been demonstrated in preclinical animal models, but there are safety concerns because of the unpredictable nature of cellular repair of double-strand breaks, as well as off-target mutagenesis. Moreover, precise knock-in of specific nucleotide changes-whether to introduce or to correct gene mutations-has proven to be inefficient in nonproliferating cells in vivo...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751570/association-of-coronary-perivascular-adipose-tissue-inflammation-and-drug-eluting-stent-induced-coronary-hyperconstricting-responses-in-pigs-18-f-fluorodeoxyglucose-positron-emission-tomography-imaging-study
#15
Kazuma Ohyama, Yasuharu Matsumoto, Hirokazu Amamizu, Hironori Uzuka, Kensuke Nishimiya, Susumu Morosawa, Michinori Hirano, Hiroshi Watabe, Yoshihito Funaki, Satoshi Miyata, Jun Takahashi, Kenta Ito, Hiroaki Shimokawa
OBJECTIVE: Although coronary perivascular adipose tissue (PVAT) may play important roles as a source of inflammation, the association of coronary PVAT inflammation and coronary hyperconstricting responses remains to be examined. We addressed this important issue in a porcine model of coronary hyperconstricting responses after drug-eluting stent implantation with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomographic imaging. APPROACH AND RESULTS: An everolimus-eluting stent (EES) was randomly implanted in pigs into the left anterior descending or the left circumflex coronary artery while nonstented coronary artery was used as a control...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751569/cyld-deubiquitinates-nicotinamide-adenine-dinucleotide-phosphate-oxidase-4-contributing-to-adventitial-remodeling
#16
Bing Yu, Ziyi Liu, Yi Fu, Yingbao Wang, Lu Zhang, Zeyu Cai, Fang Yu, Xian Wang, Jun Zhou, Wei Kong
OBJECTIVE: Transdifferentiation of adventitial fibroblasts (AFs) into myofibroblasts plays a critical role during the vascular remodeling that occurs during atherosclerosis, restenosis, and aortic aneurysm. The ubiquitination/deubiquitination regulatory system is essential for the quality control of proteins. The involvement of ubiquitination/deubiquitination during AF transdifferentiation remains largely unknown. In this study, we determined the role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF differentiation and activation in vitro and in vivo...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28751568/mtor-mechanistic-target-of-rapamycin-inhibition-decreases-mechanosignaling-collagen-accumulation-and-stiffening-of-the-thoracic-aorta-in-elastin-deficient-mice
#17
Yang Jiao, Guangxin Li, Qingle Li, Rahmat Ali, Lingfeng Qin, Wei Li, Yibing Qyang, Daniel M Greif, Arnar Geirsson, Jay D Humphrey, George Tellides
OBJECTIVE: Elastin deficiency because of heterozygous loss of an ELN allele in Williams syndrome causes obstructive aortopathy characterized by medial thickening and fibrosis and consequent aortic stiffening. Previous work in Eln-null mice with a severe arterial phenotype showed that inhibition of mTOR (mechanistic target of rapamycin), a key regulator of cell growth, lessened the aortic obstruction but did not prevent early postnatal death. We investigated the effects of mTOR inhibition in Eln-null mice partially rescued by human ELN that manifest a less severe arterial phenotype and survive long term...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729366/recommendation-on-design-execution-and-reporting-of-animal-atherosclerosis-studies-a-scientific-statement-from-the-american-heart-association
#18
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
#19
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
#20
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
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