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Genes protecting from atherosclerosis

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https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#1
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mattew, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jun Song, Rose Ackermann, Yui Koike, Anna Schwendeman, Liangxue Lai, Subramaniam Pennathur, Minerva Garcia-Barrio, Jianglin Fan, Y Eugene Chen
OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28386305/a-fermented-whole-grain-prevents-lipopolysaccharides-induced-dysfunction-in-human-endothelial-progenitor-cells
#2
Laura Giusti, Morena Gabriele, Giuseppe Penno, Monia Garofolo, Vincenzo Longo, Stefano Del Prato, Daniela Lucchesi, Laura Pucci
Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS) orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs), bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG), on early EPCs exposed to LPS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28365054/lipid-metabolism-and-emerging-targets-for-lipid-lowering-therapy
#3
REVIEW
Daniel Gaudet, Jean-Philippe Drouin-Chartier, Patrick Couture
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies to reduce the plasma levels of atherogenic lipoproteins are well established interventions that decrease CVD risk. However, treatment of dyslipidemia with the most widely used lipid-lowering drugs (ie, statins and ezetimibe) often fails to protect a significant proportion of patients from cardiovascular risk. The development of several novel therapies to treat lipid-related disorders and their associated risks is ongoing and includes the following: (1) reducing plasma levels of atherogenic lipoproteins using proprotein convertase subtilisin/kexin type 9 inhibitors, antisense inhibitors of Apolipoprotein (Apo)(a), microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides of ApoB for inhibiting very low-density lipoprotein production, and inhibitors of angiopoietin-like protein 3 or ApoC-III for triglyceride-rich lipoprotein management upstream of low-density lipoprotein production as well as gene replacement therapy to improve low-density lipoprotein and triglyceride-rich lipoprotein clearance; and (2) emerging therapies that target high-density lipoprotein (HDL) and reverse cholesterol transport using cholesteryl ester transfer protein inhibitors, HDL peptide mimetics, and autologous infusion of pre-β HDLs...
January 16, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28306170/impact-of-atrial-fibrillation-on-platelet-gene-expression
#4
Waldemar E Wysokinski, Alfonso Tafur, Naser Ammash, Samuel J Asirvatham, Yanhong Wu, Izabella Gosk-Bierska, Diane E Grill, Joshua P Slusser, Jozef Mruk, Robert D McBane
AIMS: Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR)...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28301500/circulating-progenitor-cells-in-hypertensive-subjects-effectiveness-of-a-treatment-with-olmesartan-in-improving-cell-number-and-mir-profile-in-addition-to-expected-pharmacological-effects
#5
Giuseppe Mandraffino, Caterina Oriana Aragona, Valentina Cairo, Michele Scuruchi, Alberto Lo Gullo, Angela D'Ascola, Angela Alibrandi, Saverio Loddo, Sebastiano Quartuccio, Carmela Morace, Enricomaria Mormina, Giorgio Basile, Antonino Saitta, Egidio Imbalzano
CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS)...
2017: PloS One
https://www.readbyqxmd.com/read/28298955/the-apolipoprotein-l1-gene-and-cardiovascular-disease
#6
Todd W Robinson, Barry I Freedman
Relative to those with European ancestry, African Americans have an excess incidence of nondiabetic chronic kidney disease predominantly due to two coding renal-risk variants in the apolipoprotein L1 gene (APOL1). This APOL1-kidney disease association is independent of systemic hypertension or blood pressure. Recent reports describe extra-renal effects of the APOL1 G1 and G2 renal-risk variants on cardiovascular disease (CVD), subclinical atherosclerosis, lipoprotein particle concentrations, and survival. However, results have been less consistent than those seen in kidney disease, and the observed APOL1 associations with CVD vary from risk to protective...
October 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28297582/human-stem-cell-derived-endothelial-hepatic-platform-for-efficacy-testing-of-vascular-protective-metabolites-from-nutraceuticals
#7
Balakrishnan Chakrapani Narmada, Yeek Teck Goh, Huan Li, Sanjay Sinha, Hanry Yu, Christine Cheung
Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28224128/upregulation-of-th-il-17-pathway-related-genes-in-human-coronary-endothelial-cells-stimulated-with-serum-of-patients-with-acute-coronary-syndromes
#8
Giovanni Cimmino, Loreta Pia Ciuffreda, Giovanni Ciccarelli, Paolo Calabrò, Fiorella Angelica Valeria Ferraiolo, Alessia Rivellino, Raffaele De Palma, Paolo Golino, Francesco Rossi, Plinio Cirillo, Liberato Berrino
BACKGROUND: Inflammation plays an essential role in the development and complications of atherosclerosis plaques, including acute coronary syndromes (ACS). Indeed, previous reports have shown that within the coronary circulation of ACS patients, several soluble mediators are released. Moreover, it has been demonstrated that endothelial dysfunction might play an important role in atherosclerosis as well as ACS pathophysiology. However, the mechanisms by which these soluble mediators might affect endothelial functions are still largely unknown...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28188215/cystathionine-%C3%AE-lyase-protects-vascular-endothelium-a-role-for-inhibition-of-histone-deacetylase-6
#9
Thorsten M Leucker, Yohei Nomura, Jae Hyung Kim, Anil Bhatta, Victor Wang, Andrea Wecker, Sandeep Jandu, Lakshmi Santhanam, Dan Berkowitz, Lewis Romer, Deepesh Pandey
Endothelial cystathionine γ-lyase (CSEγ) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSEγ gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSEγ. Reduced CSEγ mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE(-/-)) mice fed a high-fat diet compared with controls...
April 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28134663/sr-b1-and-pdzk1-partners-in-hdl-regulation
#10
Bernardo L Trigatti
PURPOSE OF REVIEW: To outline the roles of SR-B1 and PDZK1 in hepatic selective HDL cholesterol uptake and reverse cholesterol transport and the consequences for atherosclerosis development. RECENT FINDINGS: Much of our understanding of the physiological roles of SR-B1 and PDZK1 in HDL metabolism and atherosclerosis comes from studies of genetically manipulated mice. These show SR-B1 and PDZK1 play key roles in HDL metabolism and protection against atherosclerosis...
January 27, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#11
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089144/essential-role-of-icam-1-in-aldosterone-induced-atherosclerosis
#12
Vincenzo Marzolla, Andrea Armani, Caterina Mammi, Mary E Moss, Vittoria Pagliarini, Laura Pontecorvo, Antonella Antelmi, Andrea Fabbri, Giuseppe Rosano, Iris Z Jaffe, Massimiliano Caprio
OBJECTIVE: Elevated aldosterone is associated with increased risk of atherosclerosis complications, whereas treatment with mineralocorticoid receptor (MR) antagonists decreases the rate of cardiovascular events. Here we test the hypothesis that aldosterone promotes early atherosclerosis by modulating intercellular adhesion molecule-1 (ICAM-1) expression and investigate the molecular mechanisms by which aldosterone regulates ICAM-1 expression. METHODS AND RESULTS: Apolipoprotein-E (ApoE)(-/-) mice fed an atherogenic diet and treated with aldosterone for 4weeks showed increased vascular expression of ICAM-1, paralleled by enhanced atherosclerotic plaque size in the aortic root...
April 1, 2017: International Journal of Cardiology
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
#13
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-crystallization-in-human-atherosclerosis-is-triggered-in-smooth-muscle-cells-during-the-transition-from-fatty-streak-to-fibroatheroma
#14
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 stabilization. However, little is known about how cholesterol crystallization 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
#15
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 a previous study, we uncovered that aberrant activity of transforming growth factor β (TGF-β) signaling pathway could contribute to the vascular smooth muscle cells' (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of bone morphogenetic protein (BMP)/Smad pathway via a polyubiquitination-dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β...
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
#16
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
#17
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
#18
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
#19
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
#20
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 many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms...
January 6, 2017: Circulation Research
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