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Arteriosclerosis, Thrombosis, and Vascular Biology

Derick Okwan-Duodu, Laura Hansen, Giji Joseph, Alicia N Lyle, Daiana Weiss, David R Archer, W Robert Taylor
OBJECTIVE: The adaptive response to vascular injury is the formation of functional collateral vessels to maintain organ integrity. Many of the clinical complications associated with sickle cell disease can be attributed to repeated bouts of vascular insufficiency, yet the detailed mechanisms of collateral vessel formation after injury are largely unknown in sickle cell disease. Here, we characterize postischemic neovascularization in sickle cell disease and the role of neutrophils in the production of reactive oxygen species...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Sebhat Erqou, Jane E Clougherty, Oladipupo Olafiranye, Jared W Magnani, Aryan Aiyer, Sheila Tripathy, Ellen Kinnee, Kevin E Kip, Steven E Reis
OBJECTIVE: We aimed to assess racial differences in air pollution exposures to ambient fine particulate matter (particles with median aerodynamic diameter <2.5 µm [PM2.5 ]) and black carbon (BC) and their association with cardiovascular disease (CVD) risk factors, arterial endothelial function, incident CVD events, and all-cause mortality. APPROACH AND RESULTS: Data from the HeartSCORE study (Heart Strategies Concentrating on Risk Evaluation) were used to estimate 1-year average air pollution exposure to PM2...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Anaïs Briot, Pauline Decaunes, Fanny Volat, Chloé Belles, Muriel Coupaye, Séverine Ledoux, Anne Bouloumié
OBJECTIVE: Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function. APPROACH AND RESULTS: We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and CD36 as well as FABP4 (FA binding protein 4)...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Yuh-Charn Lin, Chun-Yu Liu, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiaofan Huang, Zhang Yue, Jia Wu, Jiuling Chen, Sihua Wang, Jie Wu, Linyun Ren, Anchen Zhang, Peng Deng, Ke Wang, Chuangyan Wu, Xiangchao Ding, Ping Ye, Jiahong Xia
OBJECTIVE: Thoracic aortic aneurysm and dissection (TAAD) are severe vascular conditions. Dysfunctional transforming growth factor-β (TGF-β) signaling in vascular smooth muscle cells and elevated angiotensin II (AngII) levels are implicated in the development of TAAD. In this study, we investigated whether these 2 factors lead to TAAD in a mouse model and explored the possibility of using microRNA-21 ( miR-21 ) for the treatment of TAAD. APPROACH AND RESULTS: TAAD was developed in Smad3 heterozygous (S3+/- ) mice infused with AngII...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Frédéric Adam, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-Claude Bordet, Jian-Dong Huang, Marijke Bryckaert, Alain Fischer, Delphine Borgel, Geneviève de Saint Basile, Olivier D Christophe, Gaël Ménasché
OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Pascal J H Kusters, Tom T P Seijkens, Linda Beckers, Dirk Lievens, Holger Winkels, Vivian de Waard, Adriaan Duijvestijn, Moritz Lindquist Liljeqvist, Joy Roy, Alan Daugherty, Andrew Newby, Norbert Gerdes, Esther Lutgens
OBJECTIVE: The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration of the aortic wall, we studied the role of the costimulatory molecule CD40L, a major driver of inflammation, in aneurysm formation. APPROACH AND RESULTS: Transcriptomics data obtained from human abdominal aortic aneurysms and normal aortas revealed increased abundance of both CD40L and CD40 in media of thrombus-free and thrombus-covered human abdominal aortic aneurysms samples...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Andrew Kimball, Matthew Schaller, Amrita Joshi, Frank Davis, Aaron denDekker, Anna Boniakowski, Jennifer Bermick, Andrea Obi, Bethany Moore, Peter K Henke, Steve L Kunkel, Katherine A Gallagher
OBJECTIVE: Wound monocyte-derived macrophage plasticity controls the initiation and resolution of inflammation that is critical for proper healing, however, in diabetes mellitus, the resolution of inflammation fails to occur. In diabetic wounds, the kinetics of blood monocyte recruitment and the mechanisms that control in vivo monocyte/macrophage differentiation remain unknown. APPROACH AND RESULTS: Here, we characterized the kinetics and function of Ly6CHi [Lin- (CD3- CD19- NK1...
March 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Sophie N Saxton, Katie E Ryding, Robert G Aldous, Sarah B Withers, Jacqueline Ohanian, Anthony M Heagerty
OBJECTIVE: Healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on resistance arteries which is vital in regulating arterial tone. Activation of β3 -adrenoceptors by sympathetic nerve-derived NA (noradrenaline) may be implicated in this effect and may stimulate the release of the vasodilator adiponectin from adipocytes. Understanding the mechanisms responsible is vital for determining how PVAT may modify vascular resistance in vivo. APPROACH AND RESULTS: Electric field stimulation profiles of healthy C57BL/6J mouse mesenteric resistance arteries were characterized using wire myography...
March 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Sarie Yamada, Takafumi Senokuchi, Takeshi Matsumura, Yutarou Morita, Norio Ishii, Kazuki Fukuda, Saiko Murakami, Shuhei Nishida, Shuji Kawasaki, Hiroyuki Motoshima, Noboru Furukawa, Yoshihiro Komohara, Yukio Fujiwara, Tomoaki Koga, Kazuya Yamagata, Motohiro Takeya, Eiichi Araki
OBJECTIVE: Macrophages play a central role in various stages of atherosclerotic plaque formation and progression. The local macrophages reportedly proliferate during atherosclerosis, but the pathophysiological significance of macrophage proliferation in this context remains unclear. Here, we investigated the involvement of local macrophage proliferation during atherosclerosis formation and progression using transgenic mice, in which macrophage proliferation was specifically suppressed...
March 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Deepesh Pandey, Yohei Nomura, Max C Rossberg, Daijiro Hori, Anil Bhatta, Gizem Keceli, Thorsten Leucker, Lakshmi Santhanam, Larissa A Shimoda, Dan Berkowitz, Lewis Romer
OBJECTIVE: KLF15 (Kruppel-like factor 15) has recently been shown to suppress activation of proinflammatory processes that contribute to atherogenesis in vascular smooth muscle, however, the role of KLF15 in vascular endothelial function is unknown. Arginase mediates inflammatory vasculopathy and vascular injury in pulmonary hypertension. Here, we tested the hypothesis that KLF15 is a critical regulator of hypoxia-induced Arg2 (arginase 2) transcription in human pulmonary microvascular endothelial cells (HPMEC)...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Akshaya K Meher, Michael Spinosa, John P Davis, Nicolas Pope, Victor E Laubach, Gang Su, Vlad Serbulea, Norbert Leitinger, Gorav Ailawadi, Gilbert R Upchurch
OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND RESULTS: NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Yang Li, Dao Wen Wang, Yundai Chen, Can Chen, Jian Guo, Shu Zhang, Zhijun Sun, Hu Ding, Yan Yao, Lei Zhou, Ke Xu, Chun Song, Fan Yang, Bin Zhao, Han Yan, Wen-Jing Wang, Chong Wu, Xiangfeng Lu, Xueli Yang, Jie Dong, Guyan Zheng, Shuhan Tian, Yanjun Cui, Lijuan Jin, Gangqiong Liu, Hanbin Cui, Shenghuang Wang, Feng Jiang, Changhua Wang, Jeanette Erdmann, Linyao Zeng, Shian Huang, Jianfeng Zhong, Yuehua Ma, Wenjiang Chen, Jianli Sun, Wei Lei, Shenghan Chen, Shaoqi Rao, Dongfeng Gu, Heribert Schunkert, Xiao-Li Tian
OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs, rs9486729 ( SCML4 ; odds ratio, 1.25; 95% CI, 1.17-1.34; P =3...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Hiroko Watase, Jie Sun, Daniel S Hippe, Niranjan Balu, Feiyu Li, Xihai Zhao, Venkatesh Mani, Zahi A Fayad, Valentin Fuster, Thomas S Hatsukami, Chun Yuan
OBJECTIVE: Early atherosclerosis is often undetected due in part to compensatory enlargement of the outer wall, termed positive remodeling. Variations in hemodynamic conditions and clinical factors influence the patterns of remodeling. The carotid artery provides an opportunity to examine these variations because of the unique geometry of the carotid bulb. This study aimed to determine differences in remodeling of the common, internal, and bifurcation segments of the carotid using magnetic resonance imaging...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Marcus Lehmann, Rogier M Schoeman, Patrick J Krohl, Alison M Wallbank, Joseph R Samaniuk, Martine Jandrot-Perrus, Keith B Neeves
OBJECTIVE: The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. APPROACH AND RESULTS: A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Elisenda Alsina-Sanchís, Yaiza García-Ibáñez, Ana M Figueiredo, Carla Riera-Domingo, Agnès Figueras, Xavier Matias-Guiu, Oriol Casanovas, Luisa M Botella, Miquel A Pujana, Antoni Riera-Mestre, Mariona Graupera, Francesc Viñals
OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell-restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF-β (transforming growth factor-β) family member. Loss-of-function mutations in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease characterized by vasculature malformations. Therapeutic strategies are aimed at reducing potential complications because of vascular malformations, but currently, there is no curative treatment for hereditary hemorrhagic telangiectasia...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Nigel Mackman, Henri M H Spronk, George A Stouffer, Hugo Ten Cate
No abstract text is available yet for this article.
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Amy C Burke, Dawn E Telford, Brian G Sutherland, Jane Y Edwards, Cynthia G Sawyez, P Hugh R Barrett, Roger S Newton, J Geoffrey Pickering, Murray W Huff
OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene targeting has been used to generate Yucatan miniature pigs heterozygous ( LDLR +/- ) or homozygous ( LDLR -/- ) for LDL receptor deficiency (ExeGen)...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiao-Bing Cui, Jun-Na Luan, Kun Dong, Sisi Chen, Yongyi Wang, Wendy T Watford, Shi-You Chen
OBJECTIVE: The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis. APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE -/- (apolipoprotein E deficient) mice and human patients. RGC-32 deficiency (Rgc32 -/- ) attenuated the high-fat diet-induced and spontaneously developed atherosclerotic lesions in ApoE -/- mice without affecting serum cholesterol concentration...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Monica Y Lee, Ana Gamez-Mendez, Jiasheng Zhang, Zhenwu Zhuang, David J Vinyard, Jan Kraehling, Heino Velazquez, Gary W Brudvig, Themis R Kyriakides, Michael Simons, William C Sessa
OBJECTIVE: The importance of PI3K/Akt signaling in the vasculature has been demonstrated in several models, as global loss of Akt1 results in impaired postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of Akt1, however, raises the possibility of cell-type-dependent Akt1-driven actions, thereby necessitating tissue-specific characterization. APPROACH AND RESULTS: Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in the vascular system...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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