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https://www.readbyqxmd.com/read/28225891/soy-milk-versus-simvastatin-for-preventing-atherosclerosis-and-left-ventricle-remodeling-in-ldl-receptor-knockout-mice
#1
L Santos, A P Davel, T I R Almeida, M R Almeida, E A Soares, G J M Fernandes, S F Magalhães, V G Barauna, J A D Garcia
Functional food intake has been highlighted as a strategy for the prevention of cardiovascular diseases by reducing risk factors. In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr-/-) fed a hyperlipidic diet. Forty 3-month old male LDLr-/- mice were distributed into four groups: control group (C), in which animals received standard diet; HL group, in which animals were fed a hyperlipidic diet; HL+SM or HL+S groups, in which animals were submitted to a hyperlipidic diet plus soy milk or simvastatin, respectively...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28220743/analysis-of-mutations-causing-familial-hypercholesterolaemia-in-black-south-african-patients-of-different-ancestr
#2
U K Ibe, R Whittall, S E Humphries, G Pilcher, F Raal
BACKGROUND: Familial hypercholesterolaemia (FH) is usually caused by mutations in three genes (LDLR, APOB and PCSK9). OBJECTIVE: To identify the spectrum of FH-causing mutations in black South African (SA) patients. METHODS: DNA samples of 16 unrelated South African FH patients with elevated low-density lipoprotein cholesterol levels, tendon xanthomas and corneal arcus (3 clinically homozygous FH and 13 heterozygous FH) of ethnic African origin were screened for mutations in the LDLR (coding region, promoter and intron/exon boundaries), APOB (part of exon 26) and PCSK9 genes (exon 7), using high-resolution melting...
January 30, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28220041/butyrate-restores-hfd-induced-adaptations-in-brain-function-and-metabolism-in-mid-adult-obese-mice
#3
I A C Arnoldussen, M Wiesmann, C E Pelgrim, E M Wielemaker, W van Duyvenvoorde, P A Santos, L Verschuren, B J F Keijser, A Heerschap, R Kleemann, P Y Wielinga, A J Kiliaan
OBJECTIVE: Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing bodyweight and adiposity. SUBJECTS: We examined the impact of a high fat diet (HFD) followed by intervention with 5% (w/w) dietary butyrate, on metabolism, microbiota, brain function and structure in the low-density-lipoprotein receptor knockout (LDLr-/-) mouse model in mid- and late life...
February 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28215318/dietary-corn-fractions-reduce-atherogenesis-in-low-density-lipoprotein-receptor-knockout-mice
#4
Kabo Masisi, Khuong Le, Nora Ghazzawi, Mohammed H Moghadasian, Trust Beta
Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root...
January 2017: Nutrition Research
https://www.readbyqxmd.com/read/28213272/rev-erb-regulation-of-cholesterologenesis
#5
Sadichha Sitaula, Jinsong Zhang, Fernanda Ruiz, Thomas P Burris
REV-ERBα and REV-ERBβ are heme regulated nuclear receptors that are known to regulate metabolic pathways. We previously demonstrated that treatment of mice with synthetic REV-ERB agonists suppressed plasma cholesterol levels and the hepatic levels of the rate limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-Mmethylglutaryl-CoA reductase). Here, we characterize the role of REV-ERB on the cholesterol biosynthetic pathway in greater detail. The REV-ERB agonist SR9009 reduced plasma cholesterol levels in both wild type C57Bl/6 and low density lipoprotein receptor (LDLR) null mice as well as reducing the expression of an array of genes within the cholesterol biosynthetic pathway...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213051/spontaneous-experimental-atherosclerosis-in-hypercholesterolemic-mice-advances-with-ageing-and-correlates-with-mitochondrial-reactive-oxygen-species
#6
Gabriel G Dorighello, Bruno A Paim, Ana Catarina Leite, Anibal E Vercesi, Helena C F Oliveira
Ageing and atherosclerosis are associated with oxidative stress. Mitochondrial redox function declines with ageing. Here we tested whether ageing LDL receptor knockout mice (LDLr(-/-)) develop spontaneous atherosclerosis and whether mitochondrial reactive oxygen species (mtROS) correlate with atherosclerosis. Compared with young mice, aged LDLr(-/-) mice exhibited 20-fold larger aortic lesion size, although the plasma cholesterol levels did not vary between age groups. The lesion sizes increased exponentially from 3 to 24months of age (r=0...
February 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28211537/ambient-ultrafine-particle-ingestion-alters-gut-microbiota-in-association-with-increased-atherogenic-lipid-metabolites
#7
Rongsong Li, Jieping Yang, Arian Saffari, Jonathan Jacobs, Kyung In Baek, Greg Hough, Muriel H Larauche, Jianguo Ma, Nelson Jen, Nabila Moussaoui, Bill Zhou, Hanul Kang, Srinivasa Reddy, Susanne M Henning, Matthew J Campen, Joseph Pisegna, Zhaoping Li, Alan M Fogelman, Constantinos Sioutas, Mohamad Navab, Tzung K Hsiai
Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp < 0.1-0.2 μm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr(-/-)) mice on a high-fat diet were orally administered with vehicle control or UFP (40 μg/mouse/day) for 3 days a week...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208647/soy-leaf-extract-exerts-atheroprotective-effects-via-modulation-of-kr%C3%A3-ppel-like-factor-2-and-adhesion-molecules
#8
Jong-Min Han, Hua Li, Moon-Hee Cho, Seung-Hwa Baek, Chul-Ho Lee, Ho-Yong Park, Tae-Sook Jeong
Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high-cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR-/-) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205325/wholegrain-oat-diet-changes-the-expression-of-genes-associated-with-intestinal-bile-acid-transport
#9
Kristina E Andersson, Aakash Chawade, Narda Thuresson, Ana Rascon, Rickard Öste, Olov Sterner, Olof Olsson, Per Hellstrand
SCOPE: The molecular mechanisms underlying the cholesterol-lowering properties of oats are only partly known. To study possible pathways involved, we investigated gene expressions in the liver and small intestine of mice fed oats. METHOD AND RESULTS: Cholesterol and bile acids were analysed in plasma and faeces from LDL-receptor deficient (LDLr(-/-) ) mice fed Western diet with wholegrain oats. A transcriptome analysis of mRNA from liver and jejunum was performed together with quantitative RT-PCR...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28205167/the-use-of-l-sidol-transgenic-mice-as-a-murine-model-to-study-hypercholesterolemia-and-atherosclerosis
#10
Eser J Zerenturk, Anna C Calkin
There are many advantages to the use of mice as a model to study the regulation of cholesterol metabolism. Common models of hypercholesterolemia include low-density lipoprotein receptor deficient (LDLR -/-) mice and apolipoprotein E deficient (ApoE) -/- mice. Herein, we describe the recently generated mouse model, L-sIDOL Tg mice, which express a dominant active form of Inducible Degrader Of the Low-density lipoprotein receptor (IDOL) in a liver-specific manner. This murine model offers significant advantages over previously established models for the study of hypercholesterolemia and atherosclerosis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28204827/hepatic-hnf1-transcription-factors-control-the-induction-of-pcsk9-mediated-by-rosuvastatin-in-normolipidemic-hamsters
#11
Bin Dong, Amar Bahadur Singh, Vikram Ravindra Shende, Jingwen Liu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) impedes low‑density lipoprotein (LDL) receptor (LDLR)-mediated LDL-cholesterol uptake and has hence emerged as a critical regulator of serum cholesterol levels and a new therapeutic target for the treatment of hypercholesterolemia. Statins have been shown to elevate circulating PCSK9 levels by stimulating PCSK9 gene transcription, which reduces the clinical efficacy of statin in LDL‑cholesterol reduction. The transcription of PCSK9 is partially controlled by the hepatocyte nuclear factor 1 (HNF1) binding site embedded in the proximal region of its promoter...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28204818/reactive-oxygen-species-mediate-angiotensin-ii-induced-transcytosis-of-low-density-lipoprotein-across-endothelial-cells
#12
Fang Bian, Jun Cui, Tao Zheng, Si Jin
The retention of plasma low-density lipoprotein (LDL) particles to subendothelial spaces through transcytosis across the endothelium is the initial step of atherosclerosis (AS). Angiotensin II (Ang II), as the principal effector molecule of the renin-angiotensin system (RAS), is implicated in several important steps of AS development. However, whether or not Ang II can directly exert a pro‑atherogenic effect by promoting LDL transcytosis across endothelial barriers, has not been defined. In the present study, we found that Ang II upregulated intracellular reactive oxygen species (ROS) levels in endothelial cells (ECs) by measuring fluorescence of 2',7'-dichlorofluorescein (DCF‑DA)...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202909/leukocyte-tlr5-deficiency-inhibits-atherosclerosis-by-reduced-macrophage-recruitment-and-defective-t-cell-responsiveness
#13
Guilielmus H J M Ellenbroek, Gijs H M van Puijvelde, Adam A Anas, Martine Bot, Miriam Asbach, Arjan Schoneveld, Peter J van Santbrink, Amanda C Foks, Leo Timmers, Pieter A Doevendans, Gerard Pasterkamp, Imo E Hoefer, Tom van der Poll, Johan Kuiper, Saskia C A de Jager
Toll-like receptors (TLR) provide a critical link between innate and adaptive immunity, both important players in atherosclerosis. Since evidence for the role of TLR5 is lacking, we aimed to establish this in the immune axis of atherosclerosis. We assessed the effect of the TLR5-specific ligand Flagellin on macrophage maturation and T-cell polarisation. Next, we generated TLR5(-/-)LDLr(-/-) chimeras to study the effect of hematopoietic TLR5 deficiency on atherosclerosis formation. Flagellin stimulation did not influence wildtype or TLR5(-/-) macrophage maturation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199412/modulation-of-cholesterol-transport-by-maternal-hypercholesterolemia-in-human-full-term-placenta
#14
Ran Zhang, Shan Dong, Wei-Wei Ma, Xue-Ping Cai, Zhi-Yin Le, Rong Xiao, Qi Zhou, Huan-Ling Yu
The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC) concentrations at third trimester higher than 7.25 mM (n = 19) and the pregnant women with normal TC concentrations (n = 19)...
2017: PloS One
https://www.readbyqxmd.com/read/28197300/long-term-treatment-of-native-ldl-induces-senescence-of-cultured-human-endothelial-cells
#15
Sung-Tack Oh, Hoon Park, Hyun Joong Yoon, Sung Yeul Yang
The study aimed to evaluate whether the treatment of primary cultured human endothelial cells with native low-density lipoprotein (nLDL) could induce their senescence and to uncover some of the putative mechanisms involved. For this purpose, human umbilical vein endothelial cells (HUVECs) were subcultured and/or continuously cultured with nLDL (0, 2, 5, and 10 μg protein/mL), for up to 9 days. The results indicated that nLDL inhibited the proliferation of HUVECs by arresting the cell cycle at G1 phase. The G1-arrested cells showed increase in cytosolic senescence-associated-β-galactosidase (SA-β-Gal) activity, a biomarker of cellular senescence...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28196290/curcumin-protects-against-intestinal-origin-endotoxemia-in-rat-liver-cirrhosis-by-targeting-pcsk9
#16
Yu Cai, Di Lu, Yanting Zou, Chaohui Zhou, Hongchun Liu, Chuantao Tu, Feng Li, Lili Liu, Shuncai Zhang
Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl4 )-induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl4 subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl4 -induced cirrhosis rats...
February 14, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28194913/vaccination-against-t-cell-epitopes-of-native-apob100-reduces-vascular-inflammation-and-disease-in-a-humanized-mouse-model-of-atherosclerosis
#17
A Gisterå, A Hermansson, D Strodthoff, M L Klement, U Hedin, G N Fredrikson, J Nilsson, G K Hansson, D F J Ketelhuth
BACKGROUND AND OBJECTIVES: The T-cell response to low-density lipoprotein (LDL) in the vessel wall plays a critical role in atherosclerotic plaque formation and stability. In this study, we used a new translational approach to investigate epitopes from human apolipoprotein B100 (ApoB100), the protein component of LDL, which triggers T-cell activation. We also evaluated the potential of two selected native ApoB100 epitopes to modulate atherosclerosis in human ApoB100-transgenic Ldlr(-/-) (HuBL) mice...
February 13, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28186192/reduced-necrosis-and-content-of-apoptotic-m1-macrophages-in-advanced-atherosclerotic-plaques-of-mice-with-macrophage-specific-loss-of-trpc3
#18
Sumeet Solanki, Prabhatchandra R Dube, Lutz Birnbaumer, Guillermo Vazquez
In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181408/epigallocatechin-gallate-induces-an-up-regulation-of-ldl-receptor-accompanied-by-a-reduction-of-pcsk9-via-the-annexin-a2-independent-pathway-in-hepg2-cells
#19
Kohei Kitamura, Yudai Okada, Kenji Okada, Yuya Kawaguchi, Satoshi Nagaoka
SCOPE: In animal studies, epigallocatechin gallate (EGCG), the dominant catechin in green tea, has been shown to improve cholesterol metabolism. However, the molecular mechanisms of EGCG underlying these functions have not been fully understood. In this study, we aimed to clarify the molecular mechanisms of the effect of EGCG on cholesterol metabolism mainly in HepG2 cells. METHODS AND RESULTS: We found that EGCG induced a reduction of the extracellular proprotein convertase subtilisin/kexin 9 (PCSK9) level accompanied by an up-regulation of the LDL receptor (LDLR) in HepG2 cells...
February 9, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28179493/nutritional-and-lipid-modulation-of-pcsk9-effects-on-cardiometabolic-risk-factors
#20
REVIEW
Jacqueline A Krysa, Teik Chye Ooi, Spencer D Proctor, Donna F Vine
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B lipoprotein cholesterol metabolism. Hepatic PCSK9 protein expression, activity, and secretion have been shown to affect cholesterol homeostasis. An upregulation of hepatic PSCK9 protein leads to increased LDLR degradation, resulting in decreased uptake of apoB lipoproteins and a consequent increase in the plasma concentration of these lipoproteins, including LDL and chylomicron remnants...
February 8, 2017: Journal of Nutrition
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