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Genes protecting from atherosclerosis

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https://www.readbyqxmd.com/read/28059114/cigarette-smoke-extract-profoundly-suppresses-tnf%C3%AE-mediated-proinflammatory-gene-expression-through-upregulation-of-atf3-in-human-coronary-artery-endothelial-cells
#1
Jack E Teasdale, Georgina G J Hazell, Alasdair M G Peachey, Graciela B Sala-Newby, Charles C T Hindmarch, Tristan R McKay, Mark Bond, Andrew C Newby, Stephen J White
Endothelial dysfunction caused by the combined action of disturbed flow, inflammatory mediators and oxidants derived from cigarette smoke is known to promote coronary atherosclerosis and increase the likelihood of myocardial infarctions and strokes. Conversely, laminar flow protects against endothelial dysfunction, at least in the initial phases of atherogenesis. We studied the effects of TNFα and cigarette smoke extract on human coronary artery endothelial cells under oscillatory, normal laminar and elevated laminar shear stress for a period of 72 hours...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039859/cholesterol-crystallisation-in-human-atherosclerosis-is-triggered-in-smooth-muscle-cells-during-the-transition-from-fatty-streak-to-fibroatheroma
#2
Benoît Ho-Tin-Noé, Sophie Vo, Richard Bayles, Stephen Ferrière, Hayette Ladjal, Sondes Toumi, Catherine Deschildre, Véronique Ollivier, Jean-Baptiste Michel
Recent studies have shown that in addition to being major constituents of the atheromatous core, solid cholesterol crystals (CCs) promote atherosclerotic lesion development and rupture by causing mechanical damage and exerting cytotoxic and pro-inflammatory effects. These findings suggest that targeting CCs might represent a therapeutic strategy for plaque stabilisation. However, little is known about how cholesterol crystallisation is initiated in human atherothrombotic disease. Here, we investigated these mechanisms...
December 31, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28029182/nedd4-deficiency-in-vascular-smooth-muscle-promotes-vascular-calcification-by-stabilizing-psmad1
#3
Ji-Hyun Lee, Seon-Ae Jeon, Byung-Gyu Kim, Michiko Takeda, Jae-Jin Cho, Dong-Ik Kim, Hiroshi Kawabe, Je-Yoel Cho
The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In previous study, we uncovered that aberrant activity of TGF-β signaling pathway could contribute the vascular smooth muscle cells (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of BMP/Smad pathway via a polyubiquitination dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β⋅ Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28012599/blood-oxidative-stress-blos-is-a-secondary-host-defense-system-responding-normally-to-anaerobic-wound-infection-and-inadvertently-to-dietary-ultra-exogenous-sulfide-formation-usf
#4
Peter G Stroot
Blood oxidative stress (BLOS) is the presence of white blood cells and platelets that are generating high levels of reactive oxygen species (ROS). A mathematical model links the level of BLOS or BLOS# and plasma sulfide concentration. An increase in the BLOS# reduces the plasma sulfide concentration. The reported maximum plasma sulfide concentration for defined health conditions were used to calculate the minimum BLOS#. Elevated BLOS generates high plasma concentration of ROS, which triggers multiple responses in the body that protect the host...
January 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/27999237/resting-and-activated-natural-tregs-decrease-in-the-peripheral-blood-of-patients-with-atherosclerosis
#5
Mohammadreza Yazdani, Shahdad Khosropanah, Ahmad Hosseini, Mehrnoosh Doroudchi
BACKGROUND: Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. OBJECTIVE: To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. METHODS: Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27927649/cilostazol-inhibits-uremic-toxin-induced-vascular-smooth-muscle-cell-dysfunction-role-of-axl-signaling
#6
Chien-Hsing Lee, Yi-Jen Hung, Yi-Shing Shieh, Chu-Yen Chien, Yu-Juei Hsu, Chih-Yuan Lin, Chi-Fu Chiang, Chia-Luen Huang, Chang-Hsun Hsieh
Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, and vascular smooth muscle cell (VSMC) dysfunction plays a pivotal role in uremic atherosclerosis. Axl signaling is involved in vascular injury and is highly expressed in VSMC. Recent reports have shown that cilostazol, a phosphodiesterase type 3 inhibitor (PDE3), can regulate various stages of the atherosclerotic process. However, the role of cilostazol in uremic vasculopathy remains unclear. This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling...
December 7, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27771368/paraoxonase-and-atherosclerosis-related-cardiovascular-diseases
#7
REVIEW
Dimitry A Chistiakov, Alexandra A Melnichenko, Alexander N Orekhov, Yuri V Bobryshev
In humans, three paraoxonase (PON1, PON2, and PON3) genes are clustered on chromosome 7 at a locus that spans a distance around 170 kb. These genes are highly homologous to each other and have a similar protein structural organization. PON2 is the intracellular enzyme, which is expressed in many tissues and organs, while two other members of PON gene family are produced by liver and associate with high density lipoprotein (HDL). The lactonase activity is the ancestral. Besides lactones and organic phosphates, PONs can hydrolyze and therefore detoxify oxidized low density lipoprotein and homocysteine thiolactone, i...
January 2017: Biochimie
https://www.readbyqxmd.com/read/27756793/microrna-181b-controls-atherosclerosis-and-aneurysms-through-regulation-of-timp-3-and-elastin
#8
Karina Di Gregoli, Nur Najmi Mohamad Anuar, Rosaria Bianco, Stephen J White, Andrew C Newby, Sarah J George, Jason L Johnson
RATIONALE: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with a number of cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm (AAA) stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates TIMP-3 expression and affects atherosclerosis and aneurysms Methods and Results: Here, we demonstrate that miR-181b was over-expressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms, and correlated with decreased expression of predicted miR-181b targets, TIMP-3 and elastin...
October 18, 2016: Circulation Research
https://www.readbyqxmd.com/read/27754186/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#9
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27725526/macrophage-apoptosis-and-efferocytosis-in-the-pathogenesis-of-atherosclerosis
#10
MacRae F Linton, Vladimir R Babaev, Jiansheng Huang, Edward F Linton, Huan Tao, Patricia G Yancey
Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes...
October 8, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27643143/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#11
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27578362/human-paraoxonase-gene-cluster-overexpression-alleviates-angiotensin-ii-induced-cardiac-hypertrophy-in-mice
#12
Jian-Fei Pei, Yun-Fei Yan, Xiaoqiang Tang, Yang Zhang, Shen-Shen Cui, Zhu-Qin Zhang, Hou-Zao Chen, De-Pei Liu
Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied...
August 30, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27566080/rrm1-rrm2-and-ercc2-gene-polymorphisms-in-coronary-artery-disease
#13
Emre Murat Altinkilic, Selim Isbir, Uzay Gormus, Seda Gulec Yilmaz, Altay Burak Dalan, Selvi Duman, Turgay Isbir
BACKGROUND/AIM: Coronary artery disease (CAD) is a chronic inflammatory disease seen as formation of atherosclerotic plaques (atheroma) in coronary arteries. Recent published papers show that DNA damage and repair mechanisms play a crucial role on the development and severity of atheromas. In this study, we investigated nucleotide excision repair (NER) pathway-related gene polymorphisms in atherosclerosis. XPD, encoded by ERCC2 gene, is an ATP-depended helicase enzyme involved in the NER pathway...
September 2016: In Vivo
https://www.readbyqxmd.com/read/27563876/transcriptional-induction-of-metallothionein-by-tris-pentafluorophenyl-stibane-in-cultured-bovine-aortic-endothelial-cells
#14
Tomoya Fujie, Masaki Murakami, Eiko Yoshida, Shuji Yasuike, Tomoki Kimura, Yasuyuki Fujiwara, Chika Yamamoto, Toshiyuki Kaji
Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells...
August 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27525442/calpain-6-confers-atherogenicity-to-macrophages-by-dysregulating-pre-mrna-splicing
#15
Takuro Miyazaki, Kazuo Tonami, Shoji Hata, Toshihiro Aiuchi, Koji Ohnishi, Xiao-Feng Lei, Joo-Ri Kim-Kaneyama, Motohiro Takeya, Hiroyuki Itabe, Hiroyuki Sorimachi, Hiroki Kurihara, Akira Miyazaki
Macrophages contribute to the development of atherosclerosis through pinocytotic deposition of native LDL-derived cholesterol in macrophages in the vascular wall. Inhibiting macrophage-mediated lipid deposition may have protective effects in atheroprone vasculature, and identifying mechanisms that potentiate this process may inform potential therapeutic interventions for atherosclerosis. Here, we report that dysregulation of exon junction complex-driven (EJC-driven) mRNA splicing confers hyperpinocytosis to macrophages during atherogenesis...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27449656/deep-transcriptomic-profiling-reveals-the-similarity-between-endothelial-cells-cultured-under-static-and-oscillatory-shear-stress-conditions
#16
Congzhen Qiao, Fan Meng, Inhwan Jang, Hanjoong Jo, Y Eugene Chen, Jifeng Zhang
Atherosclerosis is a multifactorial disease that preferentially develops in specific regions in the arterial tree. This characteristic is mainly attributed to the unique pattern of hemodynamic shear stress in vivo. High laminar shear stress (LS) found in straight lumen exerts athero-protective effects. Low or oscillatory shear stress (OS) present in regions of lesser curvature and arterial bifurcations predisposes arterial intima to atherosclerosis. Shear stress-regulated endothelial function plays an important role in the process of atherosclerosis...
September 1, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27445103/nox4-derived-reactive-oxygen-species-limit-fibrosis-and-inhibit-proliferation-of-vascular-smooth-muscle-cells-in-diabetic-atherosclerosis
#17
Elyse Di Marco, Stephen P Gray, Kit Kennedy, Cedric Szyndralewiez, Alicia N Lyle, Bernard Lassègue, Kathy K Griendling, Mark E Cooper, Harald H H W Schmidt, Karin A M Jandeleit-Dahm
Smooth muscle cell (SMC) proliferation and fibrosis contribute to the development of advanced atherosclerotic lesions. Oxidative stress caused by increased production or unphysiological location of reactive oxygen species (ROS) is a known major pathomechanism. However, in atherosclerosis, in particular under hyperglycaemic/diabetic conditions, the hydrogen peroxide-producing NADPH oxidase type 4 (NOX4) is protective. Here we aim to elucidate the mechanisms underlying this paradoxical atheroprotection of vascular smooth muscle NOX4 under conditions of normo- and hyperglycaemia both in vivo and ex vivo...
August 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27383786/ttc39b-deficiency-stabilizes-lxr-reducing-both-atherosclerosis-and-steatohepatitis
#18
Joanne Hsieh, Masahiro Koseki, Matthew M Molusky, Emi Yakushiji, Ikuyo Ichi, Marit Westerterp, Jahangir Iqbal, Robin B Chan, Sandra Abramowicz, Liana Tascau, Shunichi Takiguchi, Shizuya Yamashita, Carrie L Welch, Gilbert Di Paolo, M Mahmood Hussain, Jay H Lefkowitch, Daniel J Rader, Alan R Tall
Cellular mechanisms that mediate steatohepatitis, an increasingly prevalent condition in the Western world for which no therapies are available, are poorly understood. Despite the fact that its synthetic agonists induce fatty liver, the liver X receptor (LXR) transcription factor remains a target of interest because of its anti-atherogenic, cholesterol removal, and anti-inflammatory activities. Here we show that tetratricopeptide repeat domain protein 39B (Ttc39b, C9orf52) (T39), a high-density lipoprotein gene discovered in human genome-wide association studies, promotes the ubiquitination and degradation of LXR...
14, 2016: Nature
https://www.readbyqxmd.com/read/27381496/enhanced-base-excision-repair-capacity-in-carotid-atherosclerosis-may-protect-nuclear-dna-but-not-mitochondrial-dna
#19
Tonje Skarpengland, Tuva B Dahl, Mona Skjelland, Katja Scheffler, Mirta Mittelsted Leal de Sousa, Ida Gregersen, Anna Kuśnierczyk, Animesh Sharma, Geir Slupphaug, Lars Eide, Filip M Segers, Karolina Ryeng Skagen, Christen P Dahl, David Russell, Lasse Folkersen, Kirsten Krohg-Sørensen, Sverre Holm, Magnar Bjørås, Pål Aukrust, Bente Halvorsen
BACKGROUND: Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER and accumulation of DNA base lesions in clinical atherosclerosis is scarce. Here, we evaluated the transcriptional profile of a wide spectrum of BER components as well as DNA damage accumulation in atherosclerotic and non-atherosclerotic arteries...
August 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27349523/role-of-hesperetin-in-ldl-receptor-expression-in-hepatoma-hepg2-cells
#20
Nora A Bawazeer, Hani Choudhry, Mazin A Zamzami, Wesam H Abdulaal, Bruce Middleton, Said S Moselhy
BACKGROUND: High plasma concentration of low-density lipoprotein cholesterol (LDL-c) plays a significant role in the incidence of atherosclerosis and coronary heart diseases. The aim of this study was to investigate the mechanism by which the citrus flavonoid, hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using the human hepatoma cell line, HepG2. METHODS: Luciferase reporter gene assays were performed (in the absence of lipoprotein) to measure the activity of the LDLr promoter and the promoters of the sterol regulatory element binding protein (SREBP) transcription factors that control the LDLr promoter...
June 27, 2016: BMC Complementary and Alternative Medicine
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