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Arteriosclerosis, Thrombosis, and Vascular Biology

Bela F Asztalos, Katalin V Horvath, Ernst J Schaefer
OBJECTIVE: The cell-cholesterol efflux capacity of HDL (high-density lipoprotein) is inversely associated with coronary heart disease risk. ABCA1 (ATP-binding cassette transporter A1) plays a crucial role in cholesterol efflux from macrophages to preβ-1-HDL. We tested the hypothesis that coronary heart disease patients have functionally abnormal preβ-1-HDL. APPROACH AND RESULTS: HDL cell-cholesterol efflux capacity via the ABCA1 and the SR-BI (scavenger receptor class B type I) pathways, HDL antioxidative capacity, apo (apolipoprotein) A-I-containing HDL particles, and inflammatory- and oxidative-stress markers were measured in a case-control study of 100 coronary heart disease cases and 100 sex-matched controls...
July 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Shuai Yuan, Arif Yurdagul, Jonette M Peretik, Mabruka Alfaidi, Zaki Al Yafeai, Sibile Pardue, Christopher G Kevil, A Wayne Orr
OBJECTIVE: Flow patterns differentially regulate endothelial cell phenotype, with laminar flow promoting vasodilation and disturbed flow promoting endothelial proinflammatory activation. CSE (cystathionine γ-lyase), a major source of hydrogen sulfide (H2 S) in endothelial cells, critically regulates cardiovascular function, by both promoting vasodilation and reducing endothelial activation. Therefore, we sought to investigate the role of CSE in the endothelial response to flow. APPROACH AND RESULTS: Wild-type C57Bl/6 and CSE knockout (CSE-/- ) mice underwent carotid partial ligation to induce disturbed flow in the left carotid...
July 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Jennifer B Stott, Vincenzo Barrese, Malavika Suresh, Shirou Masoodi, Iain A Greenwood
OBJECTIVE: In renal arteries, inhibitors of G protein βγ subunits (Gβγ) reduce Kv7 activity and inhibit Kv7-dependent receptor-mediated vasorelaxations. However, the mechanisms underlying receptor-mediated relaxation are artery specific. Consequently, the aim of this study was to ascertain the role of Gβγ in Kv7-dependent vasorelaxations of the rat vasculature. APPROACH AND RESULTS: Isometric tension recording was performed in isolated rat renal, mesenteric, and cerebral arteries to study isoproterenol and calcitonin gene-related peptide relaxations...
July 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Ricardo Villa-Bellosta
OBJECTIVE: Hydroxyapatite deposition on the medial layer of the aortic walls is the hallmark of vascular calcification and the most common complication in aging individuals and in patients with diabetes mellitus and those undergoing hemodialysis. Extracellular pyrophosphate is a potent physicochemical inhibitor of hydroxyapatite crystal formation. This study analyzed changes in extracellular pyrophosphate metabolism during the phosphate-induced calcification process. APPROACH AND RESULTS: Phosphate-induced calcification of ex vivo-cultured aortic rings resulted in calcium accumulation after 7 days...
July 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Carsten Behr-Rasmussen, Jes S Lindholt, Sigitas Urbonavicius, Ulrich Halekoh, Pia Søndergaard Jensen, Jane Stubbe, Lars Melholt Rasmussen, Hans Christian Beck
OBJECTIVE: Porosity of the intraluminal thrombus (ILT) is believed to convey biologically active components from the bloodstream toward the aneurismal wall. Accumulation of molecules in the abdominal aortic aneurysmatic tissue may influence vascular protein turnover and regulate abdominal aortic aneurysm growth. We sought to identify proteins with concentrations in the ILT and the abdominal aortic aneurysm wall which associate with aneurysmal expansion rate. APPROACH AND RESULTS: Proteomic analysis by liquid chromatography tandem-mass spectrometry of separated wall and ILT samples was correlated with preoperative aneurysmal growth rate in 24 individuals operated electively for infrarenal abdominal aortic aneurysm...
July 12, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Eduardo J Folco, Thomas L Mawson, Amélie Vromman, Breno Bernardes-Souza, Grégory Franck, Oscar Persson, Momotaro Nakamura, Gail Newton, Francis W Luscinskas, Peter Libby
OBJECTIVE: Coronary artery thrombosis can occur in the absence of plaque rupture because of superficial erosion. Erosion-prone atheromata associate with more neutrophil extracellular traps (NETs) than lesions with stable or rupture-prone characteristics. The effects of NETs on endothelial cell (EC) inflammatory and thrombogenic properties remain unknown. We hypothesized that NETs alter EC functions related to erosion-associated thrombosis. APPROACH AND RESULTS: Exposure of human ECs to NETs increased VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA and protein expression in a time- and concentration-dependent manner...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Ilayaraja Muthuramu, Ruhul Amin, Joseph Pierre Aboumsallem, Mudit Mishra, Emma Louise Robinson, Bart De Geest
OBJECTIVE: We investigated the hypothesis that HDL (high-density lipoprotein) dysfunction in Scarb1 -/- mice negatively affects cardiac function both in the absence and in the presence of pressure overload. Second, we evaluated whether normalization of HDL metabolism in Scarb1 -/- mice by hepatocyte-specific SR-BI (scavenger receptor class B, type I) expression after E1E3E4-deleted adenoviral AdSR-BI (E1E3E4-deleted adenoviral vector expressing SR-BI protein in hepatocytes) transfer abrogates the effects of total body SR-BI deficiency on cardiac structure and function...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Qing Lyu, Vidhi Dhagia, Yu Han, Bing Guo, Mary E Wines-Samuelson, Christine K Christie, Qiangzong Yin, Orazio J Slivano, Paul Herring, Xiaochun Long, Sachin A Gupte, Joseph M Miano
OBJECTIVE: Unreliable antibodies often hinder the accurate detection of an endogenous protein, and this is particularly true for the cardiac and smooth muscle cofactor, MYOCD (myocardin). Accordingly, the mouse Myocd locus was targeted with 2 independent epitope tags for the unambiguous expression, localization, and activity of MYOCD protein. APPROACH AND RESULTS: 3cCRISPR (3-component clustered regularly interspaced short palindromic repeat) was used to engineer a carboxyl-terminal 3×FLAG or 3×HA epitope tag in mouse embryos...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Arash Haghikia, Xinmin S Li, Thomas G Liman, Nils Bledau, David Schmidt, Friederike Zimmermann, Nicolle Kränkel, Christian Widera, Kristina Sonnenschein, Aiden Haghikia, Karin Weissenborn, Daniela Fraccarollo, Markus M Heimesaat, Johann Bauersachs, Zeneng Wang, Weifei Zhu, Udo Bavendiek, Stanley L Hazen, Matthias Endres, Ulf Landmesser
OBJECTIVE: Gut microbiota-dependent metabolites, in particular trimethylamine N -oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Guojun Zhao, Wei Yang, Jingchun Wu, Bairu Chen, Xu Yang, Junhui Chen, David G McVey, Catherine Andreadi, Peng Gong, Tom R Webb, Nilesh J Samani, Shu Ye
OBJECTIVE: Genome-wide association studies have revealed a robust association between genetic variation on chromosome 15q26.1 and coronary artery disease (CAD) susceptibility; however, the underlying biological mechanism is still unknown. The lead CAD-associated genetic variant (rs17514846) at this locus resides in the FURIN gene. In advanced atherosclerotic plaques, furin is expressed primarily in macrophages. We investigated whether this CAD-associated variant alters FURIN expression and whether furin affects monocyte/macrophage behavior...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Virginie Joris, Elvira Leon Gomez, Lisa Menchi, Irina Lobysheva, Vittoria Di Mauro, Hrag Esfahani, Gianluigi Condorelli, Jean-Luc Balligand, Daniele Catalucci, Chantal Dessy
OBJECTIVE: Members of the microRNA (miR)-199a gene, namely miR-199a-5p and miR-199a-3p, have been recently identified as potential regulators of cardiac homeostasis. Also, upregulation of miR-199a expression in cardiomyocytes was reported to influence endothelial cells. Whether miR-199a is expressed by endothelial cells and, if so, whether it directly regulates endothelial function remains unknown. We investigate the implication of miR-199a products on endothelial function by focusing on the NOS (nitric oxide synthase)/NO pathway...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Patricia G Wilson, Joel C Thompson, Preetha Shridas, Patrick J McNamara, Maria C de Beer, Frederick C de Beer, Nancy R Webb, Lisa R Tannock
OBJECTIVE: SAA (serum amyloid A) is a family of acute-phase reactants that have proinflammatory and proatherogenic activities. SAA is more lipophilic than apoA-I (apolipoprotein A-I), and during an acute-phase response, <10% of plasma SAA is found lipid-free. In most reports, SAA is found exclusively associated with high-density lipoprotein; however, we and others have reported SAA on apoB (apolipoprotein B)-containing lipoproteins in both mice and humans. The goal of this study was to determine whether SAA is an exchangeable apolipoprotein...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Laura Z Vanags, Nathan Kum Pang Wong, Stephen James Nicholls, Christina A Bursill
Revascularization because of coronary artery disease is commonly achieved by percutaneous coronary intervention with stent deployment. Refinement in interventional techniques, major improvements in stent design (particularly drug-eluting stents), and adjunctive pharmacotherapy with dual antiplatelet regimens have led to marked reductions in the overall rates of stent failure. However, even with the advancements made in the latest generation of drug-eluting stents, unresolved biological problems persist including delayed re-endothelialization and neoatherosclerosis, which can promote late expansion of the neointima and late stent thrombosis...
June 28, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Marja G J Veugen, Ronald M A Henry, Hans-Peter Brunner-La Rocca, Pieter C Dagnelie, Miranda T Schram, Marnix J M van Agtmaal, Carla J H van der Kallen, Simone J S Sep, Martin P J van Boxtel, Otto Bekers, Steven J R Meex, Jacobus F A Jansen, Abraham A Kroon, Coen D A Stehouwer
OBJECTIVE: NT-proBNP (N-terminal pro-B-type natriuretic peptide) and cardiac troponin T (cTNT) are associated with cognitive performance. Whether this extends to individuals <60 years of age is unclear. We investigated whether age modified the associations between NT-proBNP and cTNT and cognitive performance and structural brain changes. APPROACH AND RESULTS: In 3011 individuals (60±8 years; 49% women), NT-proBNP and cTNT, memory, information processing speed and executive functioning, grey matter (GM) and white matter, and white matter hyperintensity (WMH) volumes were determined...
June 28, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Isac C Thomas, Caroline A Thompson, Mingan Yang, Matthew A Allison, Nketi I Forbang, Erin D Michos, Robyn L McClelland, Matthew J Budoff, Michael H Criqui
OBJECTIVE: Arterial calcification is highly correlated with underlying atherosclerosis. Arterial calcification of the thoracic aorta is evident in many older individuals at high susceptibility to aging-related diseases and non-cardiovascular disease (CVD)-related mortality. In this study, we evaluated the association of thoracic aorta calcification (TAC) with non-CVD morbidity and mortality. APPROACH AND RESULTS: We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical atherosclerosis, in which participants underwent cardiac computed tomography at baseline and were followed longitudinally for incident CVD events and non-CVD events...
June 28, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Wenhao Xiong, Xiangjie Zhao, Luis Villacorta, Oren Rom, Minerva T Garcia-Barrio, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jifeng Zhang, Rong Zeng, Y Eugene Chen, Zhisheng Jiang, Lin Chang
OBJECTIVE: Perivascular adipose tissue (PVAT) contributes to vascular homeostasis by producing paracrine factors. Previously, we reported that selective deletion of PPARγ (peroxisome proliferator-activated receptor γ) in vascular smooth muscle cells resulted in concurrent loss of PVAT and enhanced atherosclerosis in mice. To address the causal relationship between loss of PVAT and atherosclerosis, we used BA-PPARγ-KO (brown adipocyte-specific PPARγ knockout) mice. APPROACH AND RESULTS: Deletion of PPARγ in brown adipocytes did not affect PPARγ in white adipocytes or vascular smooth muscle cells or PPARα and PPARδ expression in brown adipocytes...
June 28, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Fleur Cohen-Aubart, Maryse Guerin, Lucie Poupel, Philippe Cluzel, Flora Saint-Charles, Frédéric Charlotte, Youssef Arsafi, Jean-François Emile, Eric Frisdal, Carine Le Goff, Jean Donadieu, Zahir Amoura, Philippe Lesnik, Julien Haroche, Wilfried Le Goff
OBJECTIVE: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by the infiltration of multiple tissues with lipid-laden histiocytes. Cardiovascular involvement is frequent in ECD and leads to a severe prognosis. The objective of this study was to determine whether an alteration of lipid metabolism participates in the lipid accumulation in histiocytes and the cardiovascular involvement in ECD. APPROACH AND RESULTS: An analysis of plasma lipid levels indicated that male ECD patients carrying the BRAF V600E mutation exhibited hypoalphalipoproteinemia, as demonstrated by low plasma HDL-C (high-density lipoprotein cholesterol) levels...
June 21, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Osamu Kurihara, Fumitaka Okajima, Masamichi Takano, Katsuhito Kato, Ryo Munakata, Daisuke Murakami, Yasushi Miyauchi, Naoya Emoto, Hitoshi Sugihara, Yoshihiko Seino, Wataru Shimizu
OBJECTIVE: Although postprandial hypertriglyceridemia can be a risk factor for coronary artery disease, the extent of its significance remains unknown. This study aimed to investigate the correlation between the postprandial lipid profiles rigorously estimated with the meal tolerance test and the presence of lipid-rich plaque, such as thin-cap fibroatheroma (TCFA), in the nonculprit lesion. APPROACH AND RESULTS: A total of 30 patients with stable coronary artery disease who underwent a multivessel examination using optical coherence tomography during catheter intervention for the culprit lesion were enrolled...
June 21, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Vincenza Caolo, Hanna M Peacock, Bahar Kasaai, Geertje Swennen, Emma Gordon, Lena Claesson-Welsh, Mark J Post, Peter Verhamme, Elizabeth A V Jones
OBJECTIVE: Vascular fusion represents an important mechanism of vessel enlargement during development; however, its significance in postnatal vessel enlargement is still unknown. During fusion, 2 adjoining vessels merge to share 1 larger lumen. The aim of this research was to identify the molecular mechanism responsible for vascular fusion. APPROACH AND RESULTS: We previously showed that both low shear stress and DAPT ( N -[ N -(3,5-difluorophenacetyl)-L-alanyl]- S -phenylglycine t-butyl ester) treatment in the embryo result in a hyperfused vascular plexus and that increasing shear stress levels could prevent DAPT-induced fusion...
June 21, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Theodora A M Claushuis, Sacha F de Stoppelaar, Alex F de Vos, Anita E Grootemaat, Nicole N van der Wel, Joris Roelofs, Jerry Ware, Cornelis Van't Veer, Tom van der Poll
OBJECTIVE: Nbeal2 -/- mice, a model of human gray platelet syndrome, have reduced neutrophil granularity and impaired host defense against systemic Staphylococcus aureus infection. We here aimed to study the role of Nbeal2 deficiency in both leukocytes and platelets during gram-negative pneumonia and sepsis. APPROACH AND RESULTS: We studied the role of Nbeal2 in platelets and leukocytes during murine pneumonia and sepsis by Klebsiella pneumoniae . Apart from platelet α-granule deficiency and reduced neutrophil granularity, also monocyte granularity was reduced in Nbeal2 -/ - mice, whereas plasma levels of MPO (myeloperoxidase), elastase, NGAL (neutrophil gelatinase-associated lipocalin), and MMP-9 (matrix metalloproteinase 9), and leukocyte CD11b expression were increased...
June 21, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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