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https://www.readbyqxmd.com/read/28859304/tilting-at-the-tilted-protease-balance-in-arterial-aneurysmal-disease
#1
Peter Libby, Galina K Sukhova, C Keith Ozaki, Guo-Ping Shi
No abstract text is available yet for this article.
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#2
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. METHODS: We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
July 13, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#3
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew Cole, Marina Beltrami-Moreira, Yiannis Chatzizisis, Thibault Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin J Croce, Peter Libby
RATIONALE: Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. OBJECTIVE: This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion...
June 23, 2017: Circulation Research
https://www.readbyqxmd.com/read/28405010/toll-like-receptor-7-deficiency-protects-apolipoprotein-e-deficient-mice-from-diet-induced-atherosclerosis
#4
Cong-Lin Liu, Marcela M Santos, Cleverson Fernandes, Mengyang Liao, Karine Iamarene, Jin-Ying Zhang, Galina K Sukhova, Guo-Ping Shi
Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine production. Increased TLR7 expression in human atherosclerotic lesions suggests its involvement in atherogenesis. Here we demonstrated TLR7 expression in macrophages, smooth muscle cells (SMCs), and endothelial cells from mouse atherosclerotic lesions. To test a direct participation of TLR7 in atherosclerosis, we crossbred TLR7-deficient (Tlr7 (-/-)) mice with apolipoprotein E-deficient (Apoe (-/-)) mice and produced Apoe (-/-) Tlr7 (-/-) and Apoe (-/-) Tlr7 (+/+) littermates, followed by feeding them an atherogenic diet to produce atherosclerosis...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#5
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-fas-lpr-mice
#6
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28033540/cathepsin-s-inhibition-changes-regulatory-t-cell-activity-in-regulating-bladder-cancer-and-immune-cell-proliferation-and-apoptosis
#7
Xiang Yan, Chun Wu, Tao Chen, Marcela M Santos, Cong-Lin Liu, Chongzhe Yang, Lijun Zhang, Jingyuan Ren, Sha Liao, Hongqiang Guo, Galina K Sukhova, Guo-Ping Shi
Regulatory T cells (Tregs) are immune suppressive cells, but their roles in tumor growth have been elusive, depending on tumor type or site. Our prior study demonstrated a role of cathepsin S (CatS) in reducing Treg immunosuppressive activity. Therefore, CatS inhibition in Tregs may exacerbate tumor growth. Using mouse bladder carcinoma MB49 cell subcutaneous implant tumor model, we detected no difference in tumor growth, whether mice were given saline- or CatS inhibitor-treated Tregs. However, mice that received inhibitor-treated Tregs had fewer splenic and tumor Tregs, and lower levels of tumor and splenic cell proliferation than mice that received saline-treated Tregs...
February 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27032103/redundancy-of-il-1-isoform-signaling-and-its-implications-for-arterial-remodeling
#8
Marina Beltrami-Moreira, Amélie Vromman, Galina K Sukhova, Eduardo J Folco, Peter Libby
AIMS: Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms α and β) have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1α and IL-1β in the induction of MMP-3 and other matrix-remodeling enzymes in human cells. METHODS AND RESULTS: Human primary vascular smooth muscle cells (VSMCs) and carotid endarterectomy specimens were stimulated with equimolar concentrations of IL-1α or IL-1β and analyzed protease expression by immunoblot and ELISA...
2016: PloS One
https://www.readbyqxmd.com/read/26898714/allergic-lung-inflammation-promotes-atherosclerosis-in-apolipoprotein-e-deficient-mice
#9
Cong-Lin Liu, Yi Wang, Mengyang Liao, Marcela M Santos, Cleverson Fernandes, Galina K Sukhova, Jin-Ying Zhang, Xiang Cheng, Chongzhe Yang, Xiaozhu Huang, Bruce Levy, Peter Libby, Gongxiong Wu, Guo-Ping Shi
Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet...
May 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/26868210/asthma-associates-with-human-abdominal-aortic-aneurysm-and-rupture
#10
RANDOMIZED CONTROLLED TRIAL
Cong-Lin Liu, Holger Wemmelund, Yi Wang, Mengyang Liao, Jes S Lindholt, Søren P Johnsen, Henrik Vestergaard, Cleverson Fernandes, Galina K Sukhova, Xiang Cheng, Jin-Ying Zhang, Chongzhe Yang, Xiaozhu Huang, Alan Daugherty, Bruce D Levy, Peter Libby, Guo-Ping Shi
OBJECTIVE: Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact. APPROACH AND RESULTS: Databases analyzed included Danish National Registry of Patients, a population-based nationwide case-control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial...
March 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26543094/allergic-lung-inflammation-aggravates-angiotensin-ii-induced-abdominal-aortic-aneurysms-in-mice
#11
Cong-Lin Liu, Yi Wang, Mengyang Liao, Holger Wemmelund, Jingyuan Ren, Cleverson Fernandes, Yi Zhou, Galina K Sukhova, Jes S Lindholt, Søren P Johnsen, Jin-Ying Zhang, Xiang Cheng, Xiaozhu Huang, Alan Daugherty, Bruce D Levy, Peter Libby, Guo-Ping Shi
OBJECTIVE: Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. APPROACH AND RESULTS: Ovalbumin sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth muscle cell loss, cell proliferation, and angiogenesis in AAA lesions...
January 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26505215/rap1-induces-cytokine-production-in-pro-inflammatory-macrophages-through-nf%C3%AE%C2%BAb-signaling-and-is-highly-expressed-in-human-atherosclerotic-lesions
#12
Yin Cai, Galina K Sukhova, Hoi Kin Wong, Aimin Xu, Vinay Tergaonkar, Paul M Vanhoutte, Eva Hoi Ching Tang
Repressor activator protein 1 (Rap1) is essential for maintaining telomere length and structural integrity, but it also exerts other non-telomeric functions. The present study tested the hypothesis that Rap1 is released into the cytoplasm and induces production of pro-inflammatory cytokines via nuclear factor kappa B (NFκB) signaling in macrophages, a cell type involved in the development and progression of atherosclerotic lesions. Western blotting analysis confirmed that Rap1 was present in the cytoplasm of differentiated human monocytic leukemia cells (THP-1, a macrophage-like cell line)...
2015: Cell Cycle
https://www.readbyqxmd.com/read/26299839/angiotensin-ii-induced-tlr4-mediated-abdominal-aortic-aneurysm-in-apolipoprotein-e-knockout-mice-is-dependent-on-stat3
#13
Zhexue Qin, Jessamyn Bagley, Galina Sukhova, Wendy E Baur, Ho-Jin Park, Debbie Beasley, Peter Libby, Yali Zhang, Jonas B Galper
Abdominal Aortic Aneurysm (AAA) is a major cause of mortality and morbidity in men over 65 years of age. Male apolipoprotein E knockout (ApoE(-/-)) mice infused with angiotensin II (AngII) develop AAA. Although AngII stimulates both JAK/STAT and Toll-like receptor 4 (TLR4) signaling pathways, their involvement in AngII mediated AAA formation is unclear. Here we used the small molecule STAT3 inhibitor, S3I-201, the TLR4 inhibitor Eritoran and ApoE(-/-)TLR4(-/-) mice to evaluate the interaction between STAT3 and TLR4 signaling in AngII-induced AAA formation...
October 2015: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26295369/deficiency-of-fc%C3%AF%C2%B5r1-increases-body-weight-gain-but-improves-glucose-tolerance-in-diet-induced-obese-mice
#14
Yun-Jung Lee, Conglin Liu, Mengyang Liao, Galina K Sukhova, Jun Shirakawa, Meriem Abdennour, Karine Iamarene, Sebastien Andre, Karen Inouye, Karine Clement, Rohit N Kulkarni, Alexander S Banks, Peter Libby, Guo-Ping Shi
Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a(-/-)) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion...
November 2015: Endocrinology
https://www.readbyqxmd.com/read/26099046/interleukin-18-function-in-atherosclerosis-is-mediated-by-the-interleukin-18-receptor-and-the-na-cl-co-transporter
#15
Jing Wang, Chongxiu Sun, Norbert Gerdes, Conglin Liu, Mengyang Liao, Jian Liu, Michael A Shi, Aina He, Yi Zhou, Galina K Sukhova, Huimei Chen, Xian Wu Cheng, Masafumi Kuzuya, Toyoaki Murohara, Jie Zhang, Xiang Cheng, Mengmeng Jiang, Gary E Shull, Shaunessy Rogers, Chao-Ling Yang, Qiang Ke, Sabina Jelen, René Bindels, David H Ellison, Petr Jarolim, Peter Libby, Guo-Ping Shi
Interleukin-18 (IL18) participates in atherogenesis through several putative mechanisms. Interruption of IL18 action reduces atherosclerosis in mice. Here, we show that absence of the IL18 receptor (IL18r) does not affect atherosclerosis in apolipoprotein E-deficient (Apoe(-/-)) mice, nor does it affect IL18 cell surface binding to or signaling in endothelial cells. As identified initially by co-immunoprecipitation with IL18, we found that IL18 interacts with the Na-Cl co-transporter (NCC; also known as SLC12A3), a 12-transmembrane-domain ion transporter protein preferentially expressed in the kidney...
July 2015: Nature Medicine
https://www.readbyqxmd.com/read/25824145/regulatory-t-cells-in-human-and-angiotensin-ii-induced-mouse-abdominal-aortic-aneurysms
#16
Yi Zhou, Wenxue Wu, Jes S Lindholt, Galina K Sukhova, Peter Libby, Xueqing Yu, Guo-Ping Shi
AIMS: Regulatory T cells (Tregs) protect mice from angiotensin II (Ang-II)-induced abdominal aortic aneurysms (AAA). This study tested whether AAA patients are Treg-insufficient and the Treg molecular mechanisms that control AAA pathogenesis. METHODS AND RESULTS: ELISA determined the Foxp3 concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P < 0...
July 1, 2015: Cardiovascular Research
https://www.readbyqxmd.com/read/25755115/tlr2-and-neutrophils-potentiate-endothelial-stress-apoptosis-and-detachment-implications-for-superficial-erosion
#17
Thibaut Quillard, Haniel Alves Araújo, Gregory Franck, Eugenia Shvartz, Galina Sukhova, Peter Libby
AIMS: Superficial erosion of atheromata causes many acute coronary syndromes, but arises from unknown mechanisms. This study tested the hypothesis that Toll-like receptor-2 (TLR2) activation contributes to endothelial apoptosis and denudation and thus contributes to the pathogenesis of superficial erosion. METHODS AND RESULTS: Toll-like receptor-2 and neutrophils localized at sites of superficially eroded human plaques. In vitro, TLR2 ligands (including hyaluronan, a matrix macromolecule abundant in eroded lesions) induced endothelial stress, characterized by reactive oxygen species production, endoplasmic reticulum (ER) stress, and apoptosis...
June 7, 2015: European Heart Journal
https://www.readbyqxmd.com/read/25510249/activation-of-prostaglandin-e2-ep4-signaling-reduces-chemokine-production-in-adipose-tissue
#18
Eva H C Tang, Yin Cai, Chi Kin Wong, Viviane Z Rocha, Galina K Sukhova, Koichi Shimizu, Ge Xuan, Paul M Vanhoutte, Peter Libby, Aimin Xu
Inflammation of adipose tissue induces metabolic derangements associated with obesity. Thus, determining ways to control or inhibit inflammation in adipose tissue is of clinical interest. The present study tested the hypothesis that in mouse adipose tissue, endogenous prostaglandin E2 (PGE2) negatively regulates inflammation via activation of prostaglandin E receptor 4 (EP4). PGE2 (5-500 nM) attenuated lipopolysaccharide-induced mRNA and protein expression of chemokines, including interferon-γ-inducible protein 10 and macrophage-inflammatory protein-1α in mouse adipose tissue...
February 2015: Journal of Lipid Research
https://www.readbyqxmd.com/read/25185259/moderate-hypoxia-potentiates-interleukin-1%C3%AE-production-in-activated-human-macrophages
#19
Eduardo J Folco, Galina K Sukhova, Thibaut Quillard, Peter Libby
RATIONALE: Inflammation drives atherogenesis. Animal and human studies have implicated interleukin-1β (IL-1β) in this disease. Moderate hypoxia, a condition that prevails in the atherosclerotic plaque, may conspire with inflammation and contribute to the evolution and complications of atherosclerosis through mechanisms that remain incompletely understood. OBJECTIVE: This study investigated the links between hypoxia and inflammation by testing the hypothesis that moderate hypoxia modulates IL-1β production in activated human macrophages...
October 24, 2014: Circulation Research
https://www.readbyqxmd.com/read/25170063/increased-microvascularization-and-vessel-permeability-associate-with-active-inflammation-in-human-atheromata
#20
Viviany R Taqueti, Marcelo F Di Carli, Michael Jerosch-Herold, Galina K Sukhova, Venkatesh L Murthy, Eduardo J Folco, Raymond Y Kwong, C Keith Ozaki, Michael Belkin, Matthias Nahrendorf, Ralph Weissleder, Peter Libby
BACKGROUND: Studies have shown the feasibility of imaging plaques with 2-deoxy-2-[(18)F]fluoroglucose (FDG) positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging with inconsistent results. We sought to investigate the relationship between markers of inflammatory activation, plaque microvascularization, and vessel wall permeability in subjects with carotid plaques using a multimodality approach combining FDG positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging, and histopathology...
November 2014: Circulation. Cardiovascular Imaging
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