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Galina sukhova

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
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
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
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
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
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
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
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
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
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
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
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
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
Jing Wang, Sara Sjöberg, Ting-Ting Tang, Katariina Oörni, Wenxue Wu, Conglin Liu, Blandine Secco, Viviane Tia, Galina K Sukhova, Cleverson Fernandes, Adam Lesner, Petri T Kovanen, Peter Libby, Xiang Cheng, Guo-Ping Shi
Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3months. When mice consume this diet for 6months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels...
November 2014: Biochimica et Biophysica Acta
Jing Wang, Galina K Sukhova, Jian Liu, Keith Ozaki, Adam Lesner, Peter Libby, Petri T Kovanen, Guo-Ping Shi
OBJECTIVE: Cathepsin G (CatG) is a serine protease that mediates angiotensin I to angiotensin II (Ang-II) conversion and is highly expressed in human abdominal aortic aneurysms (AAAs). However, it remains untested whether this protease participates in the pathogenesis of AAA. METHODS AND RESULTS: Immunofluorescent double staining demonstrated the expression of CatG in smooth muscle cells (SMCs), macrophages, and endothelial cells in human AAA lesions (n = 12) but not in AAA-free aortas (n = 10)...
December 2015: Journal of Vascular Surgery
Jing Wang, Jes S Lindholt, Galina K Sukhova, Michael A Shi, Mingcan Xia, Han Chen, Meixiang Xiang, Aina He, Yi Wang, Na Xiong, Peter Libby, Jian-An Wang, Guo-Ping Shi
Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD8+ T cells. IgE induces CD4+ T-cell production of IL6 and IFN-γ, but reduces their production of IL10. FcεR1 deficiency (Fcer1a-/-) protects apolipoprotein E-deficient (Apoe-/-) mice from angiotensin-II infusion-induced AAAs and reduces plasma IL6 levels...
July 2014: EMBO Molecular Medicine
Viviane Zorzanelli Rocha, Eduardo J Folco, Cafer Ozdemir, Yuri Sheikine, Thomas Christen, Galina K Sukhova, Eva H C Tang, Marcio Sommer Bittencourt, Raul D Santos, Andrew D Luster, David E Cohen, Peter Libby
OBJECTIVE: Obesity associates with increased numbers of inflammatory cells in adipose tissue (AT), including T cells, but the mechanism of T-cell recruitment remains unknown. This study tested the hypothesis that the chemokine (C-X-C motif) receptor 3 (CXCR3) participates in T-cell accumulation in AT of obese mice and thus in the regulation of local inflammation and systemic metabolism. APPROACH AND RESULTS: Obese wild-type mice exhibited higher mRNA expression of CXCR3 in periepididymal AT-derived stromal vascular cells compared with lean mice...
July 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Ingo Hilgendorf, Igor Theurl, Louisa M S Gerhardt, Clinton S Robbins, Georg F Weber, Ayelet Gonen, Yoshiko Iwamoto, Norbert Degousee, Tobias A W Holderried, Carla Winter, Andreas Zirlik, Herbert Y Lin, Galina K Sukhova, Jagdish Butany, Barry B Rubin, Joseph L Witztum, Peter Libby, Matthias Nahrendorf, Ralph Weissleder, Filip K Swirski
BACKGROUND: Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other's function and shape the course of disease can illuminate our understanding of atherosclerosis. Innate response activator (IRA) B cells are a recently described population of granulocyte macrophage colony-stimulating factor-secreting cells of hitherto unknown function in atherosclerosis...
April 22, 2014: Circulation
Xinghui Sun, Shaolin He, A K M Wara, Basak Icli, Eugenia Shvartz, Yevgenia Tesmenitsky, Nathan Belkin, Dazhu Li, Timothy S Blackwell, Galina K Sukhova, Kevin Croce, Mark W Feinberg
RATIONALE: Activated nuclear factor (NF)-κB signaling in the vascular endothelium promotes the initiation and progression of atherosclerosis. Targeting endothelial NF-κB may provide a novel strategy to limit chronic inflammation. OBJECTIVE: To examine the role of microRNA-181b (miR-181b) in endothelial NF-κB signaling and effects on atherosclerosis. METHODS AND RESULTS: MiR-181b expression was reduced in the aortic intima and plasma in apolipoprotein E-deficient mice fed a high-fat diet...
January 3, 2014: Circulation Research
Anastasia A Borodinova, Denis V Abramochkin, Galina S Sukhova
In the mammalian myocardium, ACh, which is the main neurotransmitter of cardiac parasympathetic postganglionic fibres, can be released via both quantal (vesicular) and non-quantal (non-vesicular) mechanisms of secretion. Non-quantal release is continuous and independent of vagus activity and exocytosis of ACh-containing vesicles. During the incubation of myocardium in the presence of acetylcholinesterase (AChE) inhibitors, non-quantal ACh release leads to accumulation of ACh in the myocardium and cholinergic effects, which are proportional to the intensity of non-quantal secretion...
December 2013: Experimental Physiology
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