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Atherosclerosis pathology

Alice Ossoli, Chiara Pavanello, Eleonora Giorgio, Laura Calabresi, Monica Gomaraschi
Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection...
March 15, 2018: Current Medicinal Chemistry
Sanjay Tewari, George Renney, John Brewin, Kate Gardner, Fenella Kirkham, Baba Inusa, James E Barrett, Stephan Menzel, Swee Lay Thein, Malcolm Ward, David C Rees
Silent cerebral infarction is the commonest neurological abnormality in children with sickle cell anemia, affecting 30-40% 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS)...
March 15, 2018: Haematologica
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Marie Madsen, Peter Riis Hansen, Lars Bo Nielsen, Renata Martins Cardoso, Miranda van Eck, Tanja Xenia Pedersen
Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates interleukin-17-dependent pathologies in mice...
March 12, 2018: American Journal of Pathology
Hui Zhu, Zhixing Li, Jinglei Lv, Renliang Zhao
OBJECTIVE: Cerebral small vessel disease (CSVD) describes a syndrome of neuroimaging, pathological, and associated clinical features caused by small intracranial vascular lesions, which commonly coexists with large artery atherosclerosis (LAA) and has been identified as a major cause of motor impairment over time. In this review, we aim to summarize the relationship between CSVD and LAA, and discuss the effects of CSVD on the clinical outcome of patients with ischemic stroke caused by LAA...
March 15, 2018: Neurological Research
Wengao Jiang, Qiang Tang, Lei Zhang, Yinxue Chao, Bing Hong
OBJECTIVE: Recent studies have indicated the implication of C1q tumour necrosis factor-related protein 9 in vascular pathology of atherosclerosis. This study first investigated the association of C1q tumour necrosis factor-related protein 9 and the severity of lower extremity peripheral arterial disease in type 2 diabetes mellitus patients. METHODS: A total of 200 patients with type 2 diabetes mellitus had ankle-brachial index examined in this cross-sectional study, 60 patients with ankle-brachial index of ⩽0...
March 1, 2018: Diabetes & Vascular Disease Research
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Sarah A Aroner, Manja Koch, Kenneth J Mukamal, Jeremy D Furtado, James H Stein, Matthew C Tattersall, Robyn L McClelland, Majken K Jensen
BACKGROUND: Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology. METHODS AND RESULTS: We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III-defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002)...
March 14, 2018: Journal of the American Heart Association
Masoud Tajamolian, Parisa Kolahdouz, Parvaneh Nikpour, Seyed Khalil Forouzannia, Mohammad Hasan Sheikhha, Ehsan Farashahi Yazd
Background: Familial hypercholesterolemia (FH) is a disorder that is inherited by autosomal dominant pattern. The main cause of FH disease is the occurrence of mutations in low-density lipoprotein receptor (LDLR) gene sequence, as well as apolipoprotein B and proprotein convertase subtilisin/kexin type 9 genes, located in the next ranks, respectively. Materials and Methods: Forty-five unrelated Iranian patients with FH were screened using a high-resolution melting (HRM) method for exon 9 along with intron/exon boundaries of LDLR gene...
2018: Advanced Biomedical Research
Bing Yang, Huili Zhu, Yusheng Zhang, Anding Xu
Intracranial branch atheromatous disease is an atheromatous pathophysiological process associated with occlusion or stenosis at the orifice of a deep penetrating artery. However, apart from autopsy, atherosclerosis in the penetrating artery has not been confirmed in vivo. In this case, we confirmed that the ostium was located in the parent artery plaque and demonstrated the atherosclerosis of the proximal penetrating artery by using high-resolution magnetic resonance imaging. HR-MRI can be used to identify the pathological changes in penetrating arteries and provides more reliable basic information for the clinical subclassification and optimal medical treatment of penetrating artery infarction...
March 9, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Xue-Na Zheng, Jun Yang, Tao Xie, Bin Guo, Zhi-Qiang Xie, Li-Na Xie, Xue-Fen Wu, Gang-Zhu Hu, Mai-Lan Liu, Zeng-Hui Yue
OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups( n =12 rabbits in each group)...
February 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Jin Gu Cho, Aram Lee, Woochul Chang, Myeong-Sok Lee, Jongmin Kim
Endothelial cells that line the inner walls of blood vessels are in direct contact with blood and display remarkable heterogeneity in their response to exogenous stimuli. These ECs have unique location-dependent properties determined by the corresponding vascular beds and play an important role in regulating the homeostasis of the vascular system. Evidence suggests that vascular endothelial cells exposed to various environments undergo dynamic phenotypic switching, a key biological program in the context of endothelial heterogeneity, but that might result in EC dysfunction and, in turn, cause a variety of human diseases...
2018: Frontiers in Immunology
Michael J Hurley, Robert M J Deacon, Katrin Beyer, Elena Ioannou, Agustin Ibáñez, Jessica L Teeling, Patricia Cogram
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disease. Despite decades of research, no disease modifying therapy is available and a change of research objectives and/or development of novel research tools may be required. Much AD research has been based on experimental models using animals with a short lifespan that have been extensively genetically manipulated and do not represent the full spectrum of late-onset AD, which make up the majority of cases. The aetiology of AD is heterogeneous and involves multiple factors associated with the late-onset of the disease like disturbances in brain insulin, oxidative stress, neuroinflammation, metabolic syndrome, retinal degeneration and sleep disturbances which are all progressive abnormalities that could account for many molecular, biochemical and histopathological lesions found in brain from patients dying from AD...
March 4, 2018: Pharmacology & Therapeutics
Dasha Fuentes, Nidia Fernández, Yenela García, Teidy García, Ana Ruth Morales, Roberto Menéndez
The knockout mouse model, B6.129P2-Apoetm1Unc is homozygotic for the Apolipoprotein E (ApoE) deletion; thus, it is capable of developing hyperlipidemia and atherosclerosis but ApoE is also a lipid-transport protein abundantly expressed in most neurons in the central nervous system, so these animals could also be models of neurodegenerative diseases. The aim of this study was to determine age-related changes in spontaneous behavior and in learning and memory of Apolipoprotein E knockout mice. Spontaneous behavioral measurements included sleeping pattern, motor coordination and balance by rotarod and open field activity, whereas learning and memory tests included forced alternation in Y-maze, novel object recognition and passive avoidance conditioning...
March 3, 2018: Behavioral Sciences
Luca Parisi, Elisabetta Gini, Denisa Baci, Marco Tremolati, Matteo Fanuli, Barbara Bassani, Giampietro Farronato, Antonino Bruno, Lorenzo Mortara
Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states...
2018: Journal of Immunology Research
Zhen-Yu Yao, Wen-Bin Chen, Shan-Shan Shao, Shi-Zhan Ma, Chong-Bo Yang, Meng-Zhu Li, Jia-Jun Zhao, Ling Gao
Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells...
2018: Journal of Zhejiang University. Science. B
Hong Jin, Daniel Y Li, Ekaterina Chernogubova, Changyan Sun, Albert Busch, Suzanne M Eken, Peter Saliba-Gustafsson, Hanna Winter, Greg Winski, Uwe Raaz, Isabel N Schellinger, Nancy Simon, Renate Hegenloh, Ljubica Perisic Matic, Maja Jagodic, Ewa Ehrenborg, Jaroslav Pelisek, Hans-Henning Eckstein, Ulf Hedin, Alexandra Backlund, Lars Maegdefessel
miRNAs are potential regulators of carotid artery stenosis and concordant vulnerable atherosclerotic plaques. Hence, we analyzed miRNA expression in laser captured micro-dissected fibrous caps of either ruptured or stable plaques (n = 10 each), discovering that miR-21 was significantly downregulated in unstable lesions. To functionally evaluate miR-21 in plaque vulnerability, miR-21 and miR-21/apolipoprotein-E double-deficient mice (Apoe-/- miR-21-/- ) were assessed. miR-21-/- mice lacked sufficient smooth muscle cell proliferation in response to carotid ligation injury...
January 31, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Magda R Hamczyk, Ricardo Villa-Bellosta, Pilar Gonzalo, María J Andrés-Manzano, Paula Nogales, Jacob F Bentzon, Carlos López-Otín, Vicente Andrés
Background -Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). HGPS patients with ubiquitous progerin expression exhibit accelerated aging and atherosclerosis, and die in their early teens mainly from myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part due to the lack of appropriate animal models. Methods -We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient ( Apoe-/- ) mice with LmnaG609G/G609G mice ubiquitously expressing progerin...
February 28, 2018: Circulation
Anton G Kutikhin, Maxim Yu Sinitsky, Arseniy E Yuzhalin, Elena A Velikanova
Among applicable high-throughput techniques in cardiovascular biology, whole-transcriptome sequencing is of particular use. By utilizing RNA that is isolated from virtually all cells and tissues, the entire transcriptome can be evaluated. In comparison with other high-throughput approaches, RNA sequencing is characterized by a relatively low-cost and large data output, which permits a comprehensive analysis of spatiotemporal variation in the gene expression profile. Both shear stress and cyclic strain exert hemodynamic force upon the arterial endothelium and are considered to be crucial determinants of endothelial physiology...
February 21, 2018: High Throughput
Wanyue Xu, Yaping Pan, Qiufang Xu, Yun Wu, Jiayu Pan, Jingya Hou, Li Lin, Xiaolin Tang, Chen Li, Jingbo Liu, Dongmei Zhang
BACKGROUND: Porphyromonas gingivalis (P. gingivalis), one of the main pathogenic bacteria involved in periodontitis, induces the expression of intercellular adhesion molecule - 1 (ICAM-1) and monocyte-endothelial cell adhesion. This effect plays a pivotal role in atherosclerosis development. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and critically affects atherosclerosis pathogenesis. In this study, we tested the involvement of MIF in the P. gingivalis ATCC 33277-enhanced adhesive properties of endothelial cells...
February 26, 2018: BMC Microbiology
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