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atherosclerosis development

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https://www.readbyqxmd.com/read/28735291/subclinical-atherosclerosis-cardiac-and-kidney-function-heart-failure-and-dementia-in-the-very-elderly
#1
Lewis H Kuller, Oscar L Lopez, John S Gottdiener, Dalane W Kitzman, James T Becker, Yuefang Chang, Anne B Newman
BACKGROUND: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury)...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28735290/membrane-tethered-metalloproteinase-expressed-by-vascular-smooth-muscle-cells-limits-the-progression-of-proliferative-atherosclerotic-lesions
#2
Richard H Barnes, Takeshi Akama, Miina K Öhman, Moon-Sook Woo, Julian Bahr, Stephen J Weiss, Daniel T Eitzman, Tae-Hwa Chun
BACKGROUND: The MMP (matrix metalloproteinase) family plays diverse and critical roles in directing vascular wall remodeling in atherosclerosis. Unlike secreted-type MMPs, a member of the membrane-type MMP family, MT1-MMP (membrane-type 1 MMP; MMP14), mediates pericellular extracellular matrix degradation that is indispensable for maintaining physiological extracellular matrix homeostasis. However, given the premature mortality exhibited by MT1-MMP-null mice, the potential role of the proteinase in atherogenesis remains elusive...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28733363/lipidomic-profiling-of-patient-specific-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells
#3
Mostafa Kiamehr, Leena E Viiri, Terhi Vihervaara, Kaisa M Koistinen, Mika Hilvo, Kim Ekroos, Reijo Käkelä, Katriina Aalto-Setälä
Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model for primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a 3-step protocol through definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid metabolism-related genes were performed during the entire differentiation process from iPSC to HLCs...
July 21, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28733245/engineered-nanoparticles-for-the-detection-treatment-and-prevention-of-atherosclerosis-how-close-are-we
#4
REVIEW
Luong T H Nguyen, Aristo Muktabar, Jinkai Tang, Vinayak P Dravid, C Shad Thaxton, Subbu Venkatraman, Kee Woei Ng
Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. Nanotechnology has provided the possibility of designing nanoparticles that can translocate through tissues and home in to atherosclerotic plaques to achieve desired diagnostic, therapeutic, theranostic or 'theralivery' outcomes. Although nanomedicine approaches have demonstrated exciting possibilities, clinical reality is still distant and challenges are aplenty, such as specificity of targeting and nanotoxicity. Nevertheless, developments in formulations, delivery strategies and experimental models over the coming years will generate new knowledge to define the true potential of this field...
July 18, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28730752/targeted-nanotherapeutics-encapsulating-liver-x-receptor-agonist-gw3965-enhance-antiatherogenic-effects-without-adverse-effects-on-hepatic-lipid-metabolism-in-ldlr-mice
#5
Mikyung Yu, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw, Seung-Joo Lee, Kevin Si, Carleena Angelica Ortega, Won Il Choi, In-Hyun Lee, Yazan Bdour, Jinjun Shi, Morteza Mahmoudi, Sangyong Jon, Edward A Fisher, Omid C Farokhzad
The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized...
July 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28729366/recommendation-on-design-execution-and-reporting-of-animal-atherosclerosis-studies-a-scientific-statement-from-the-american-heart-association
#6
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/28729353/recommendation-on-design-execution-and-reporting-of-animal-atherosclerosis-studies-a-scientific-statement-from-the-american-heart-association
#7
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: Circulation Research
https://www.readbyqxmd.com/read/28729181/expression-of-cyp4v2-in-human-thp1-macrophages-and-its-transcriptional-regulation-by-peroxisome-proliferator-activated-receptor-gamma
#8
Myeongjin Yi, Jae-Gook Shin, Su-Jun Lee
Because macrophages respond to a variety of pathological and pharmacological reagents, understanding the role of P450s in macrophages is important for therapeutic intervention. There has been a lack of research on CYP4 in macrophages, but fatty acid accumulation and lipid trafficking in macrophages have been suggested to be a main cause of atherosclerosis. All human CYP4 genes (n=12) were screened in THP1 macrophages by gene-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Only CYP4V2 exhibited strong expression of both mRNA and protein...
July 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28728140/effects-of-inorganic-arsenic-methylated-arsenicals-and-arsenobetaine-on-atherosclerosis-in-the-mouse-model-and-the-role-of-as3mt-mediated-methylation
#9
Luis Fernando Negro Silva, Maryse Lemaire, Catherine A Lemarié, Dany Plourde, Alicia M Bolt, Christopher Chiavatti, D Scott Bohle, Vesna Slavkovich, Joseph H Graziano, Stéphanie Lehoux, Koren K Mann
BACKGROUND: Arsenic is metabolized through a series of oxidative methylation reactions by arsenic (3) methyltransferase (As3MT) to yield methylated intermediates. Although arsenic exposure is known to increase the risk of atherosclerosis, the contribution of arsenic methylation and As3MT remains undefined. OBJECTIVES: Our objective was to define whether methylated arsenic intermediates were proatherogenic and whether arsenic biotransformation by As3MT was required for arsenic-enhanced atherosclerosis...
July 5, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28728107/developing-potential-agents-against-atherosclerosis-design-synthesis-and-pharmacological-evaluation-of-novel-dual-inhibitors-of-oxidative-stress-and-squalene-synthase-activity
#10
Maria G Katselou, Alexios N Matralis, Angeliki P Kourounakis
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727835/conflicting-relationship-between-age-dependent-disorders-valvular-heart-disease-and-coronary-artery-disease-by-covariance-structure-analysis-possible-contribution-of-natriuretic-peptide
#11
Risa Fukumoto, Makoto Kawai, Kosuke Minai, Kazuo Ogawa, Jun Yoshida, Yasunori Inoue, Satoshi Morimoto, Toshikazu Tanaka, Tomohisa Nagoshi, Takayuki Ogawa, Michihiro Yoshimura
BACKGROUND: It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development...
2017: PloS One
https://www.readbyqxmd.com/read/28726978/analysis-of-the-substrate-specificity-of-factor-vii-activating-protease-fsap-and-design-of-specific-and-sensitive-peptide-substrates
#12
Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L Schneider, Charles S Craik, Sandip Kanse
Factor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28724840/exposure-to-parental-smoking-in-childhood-is-associated-with-high-c-reactive-protein-in-adulthood-the-cardiovascular-risk-in-young-finns-study
#13
Di Wang, Markus Juonala, Jorma S A Viikari, Feitong Wu, Nina Hutri-Kähönen, Olli T Raitakari, Costan G Magnussen
AIM: Children exposed to parental smoking are at increased long-term risk of subclinical atherosclerosis in adulthood. However, it has not been quantified if exposure to parental smoking in childhood is associated with adult systemic inflammation. This study aimed to determine if childhood exposure to parental smoking was associated with high-sensitivity C-reactive protein (hsCRP) in adulthood. METHODS: This longitudinal analysis of 2,511 participants used data from the Cardiovascular Risk in Young Finns Study, a prospective cohort of Finnish children...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28724635/heterodimers-of-the-transcriptional-factors-nfatc3-and-fosb-mediate-tissue-factor-expression-for-15-s-hydroxyeicosatetraenoic-acid-induced-monocyte-trafficking
#14
Sivareddy Kotla, Nikhlesh K Singh, Daniel Kirchhofer, Gadiparthi N Rao
Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28723693/upregulation-of-microrna-876-induces-endothelial-cell-apoptosis-by-suppressing-bcl-xl-in-development-of-atherosclerosis
#15
Kaicheng Xu, Peng Liu, Yue Zhao
BACKGROUND/AIMS: The injury and apoptotic cell death of endothelial cells hallmark the development of atherosclerosis (AS), characterized by dysregulation of lipid homeostasis, immune responses, and formation of coronary plaques. However, the mechanisms underlying the initiation of endothelial cell apoptosis remain ill-defined. Recent evidence suggests a role of microRNAs in the processes of AS-associated endothelial cell apoptosis. Thus, we studied this question in the current study...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28721155/clinical-importance-of-epicardial-adipose-tissue
#16
Eszter Nagy, Adam L Jermendy, Bela Merkely, Pal Maurovich-Horvat
Different visceral fat compartments have several systemic effects and may play a role in the development of both insulin resistance and cardiovascular diseases. In the last couple of years special attention has been paid to the epicardial adipose tissue (EAT), which can be quantified by non-invasive cardiac imaging techniques. The epicardial fat is a unique fat compartment between the myocardium and the visceral pericardium sharing a common embryologic origin with the visceral fat depot. Epicardial adipose tissue has several specific roles, and its local effects on cardiac function are incorporated in the complex pathomechanism of coronary artery disease...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28721154/obesity-and-inflammation-the-linking-mechanism-and-the-complications
#17
Mohammed S Ellulu, Ismail Patimah, Huzwah Khaza'ai, Asmah Rahmat, Yehia Abed
Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28720870/monocyte-adhesion-to-atherosclerotic-matrix-proteins-is-enhanced-by-asn-gly-arg-deamidation
#18
Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720427/the-challenges-and-promise-of-targeting-the-liver-x-receptors-for-treatment-of-inflammatory-disease
#19
REVIEW
Michael B Fessler
The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720123/cardiovascular-magnetic-resonance-in-an-adult-human-population-serial-observations-from-the-multi-ethnic-study-of-atherosclerosis
#20
REVIEW
Kihei Yoneyama, Bharath A Venkatesh, David A Bluemke, Robyn L McClelland, João A C Lima
The Multi-Ethnic Study of Atherosclerosis (MESA) is the first large-scale multi-ethnic population study in the U.S. to use advanced cardiovascular magnetic resonance (CMR) imaging. MESA participants were free of cardiovascular disease at baseline between 2000 and 2002, and were followed up between 2009 and 2011 with repeated CMR examinations as part of MESA. CMR allows the clinician to visualize and accurately quantify volume and dimensions of all four cardiac chambers; measure systolic and diastolic ventricular function; assess myocardial fibrosis; assess vessel lumen size, vessel wall morphology, and vessel stiffness...
July 18, 2017: Journal of Cardiovascular Magnetic Resonance
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