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Genes protecting from atherosclerosis

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https://www.readbyqxmd.com/read/27771368/paraoxonase-and-atherosclerosis-related-cardiovascular-diseases
#1
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...
October 19, 2016: Biochimie
https://www.readbyqxmd.com/read/27756793/microrna-181b-controls-atherosclerosis-and-aneurysms-through-regulation-of-timp-3-and-elastin
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27525442/calpain-6-confers-atherogenicity-to-macrophages-by-dysregulating-pre-mrna-splicing
#9
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
#10
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
#11
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
#12
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...
July 6, 2016: Nature
https://www.readbyqxmd.com/read/27381496/enhanced-base-excision-repair-capacity-in-carotid-atherosclerosis-may-protect-nuclear-dna-but-not-mitochondrial-dna
#13
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
#14
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...
2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27338244/interaction-between-polyphenols-intake-and-pon1-gene-variants-on-markers-of-cardiovascular-disease-a-nutrigenetic-observational-study
#15
Federica Rizzi, Costanza Conti, Elena Dogliotti, Annalisa Terranegra, Erika Salvi, Daniele Braga, Flavia Ricca, Sara Lupoli, Alessandra Mingione, Francesca Pivari, Caterina Brasacchio, Matteo Barcella, Martina Chittani, Francesca D'Avila, Maurizio Turiel, Monica Lazzaroni, Laura Soldati, Daniele Cusi, Cristina Barlassina
BACKGROUND: Paraoxonase 1 (PON1) gene polymorphisms and polyphenols intake have been reported independently associated to lipid profile and susceptibility to atherosclerosis and cardiovascular disease. However, the interaction between these factors remains to be investigated. We performed an observational nutrigenetic study to examine whether the interaction between polyphenols and anthocyanins intake and PON1 genetic variants can modulate biomarkers of cardiovascular health in an Italian healthy population...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27323195/ursodeoxycholic-acid-upregulates-erk-and-akt-in-the-protection-of-cardiomyocytes-against-cocl2
#16
N I Hanafi, A S Mohamed, J Md Noor, N Abdu, Hamid Hasani, R Siran, N J Osman, S Ab Rahim, S H Sheikh Abdul Kadir
Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia...
2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27318926/autophagic-effects-of-hibiscus-sabdariffa-leaf-polyphenols-and-epicatechin-gallate-ecg-against-oxidized-ldl-induced-injury-of-human-endothelial-cells
#17
Jing-Hsien Chen, Ming-Shih Lee, Chi-Ping Wang, Cheng-Chin Hsu, Hui-Hsuan Lin
PURPOSE: Oxidized low-density lipoprotein (ox-LDL) contributes to the pathogenesis of atherosclerosis by promoting vascular endothelial cell injury. Hibiscus sabdariffa leaf polyphenols (HLP), rich in flavonoids, have been shown to possess antioxidant and antiatherosclerotic activities. In this study, we examined the protective role of HLP and its main compound (-)-epicatechin gallate (ECG) in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL in vitro. METHODS: In a model of ox-LDL-impaired HUVECs, assessments of cell viability, cytotoxicity, cell proliferation, apoptosis, and autophagy were detected...
June 18, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27252422/telomere-length-and-coronary-atherosclerosis-in-rheumatoid-arthritis
#18
Michelle J Ormseth, Joseph F Solus, Annette M Oeser, Aihua Bian, Tebeb Gebretsadik, Ayumi Shintani, Paolo Raggi, C Michael Stein
OBJECTIVE: Telomeres protect against chromosomal end damage and shorten with each cell division; their length may be a marker of cardiovascular and overall biological aging. We examined the hypothesis that reduced telomere length is associated with increased coronary atherosclerosis in rheumatoid arthritis (RA). METHODS: We performed a cross-sectional study in 145 patients with RA and 87 control subjects frequency-matched for age, race, and sex. Coronary artery calcium score was determined by noncontrast cardiac computed tomography...
August 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27249230/sirt6-protects-against-endothelial-dysfunction-and-atherosclerosis-in-mice
#19
Suowen Xu, Meimei Yin, Marina Koroleva, Michael A Mastrangelo, Wenbo Zhang, Peter Bai, Peter J Little, Zheng Gen Jin
SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE(-/-) mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation...
May 2016: Aging
https://www.readbyqxmd.com/read/27238723/paraoxonases-1-2-and-3-what-are-their-functions
#20
Clement E Furlong, Judit Marsillach, Gail P Jarvik, Lucio G Costa
Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer...
November 25, 2016: Chemico-biological Interactions
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