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hypercholesterolemia without atherosclerosis

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https://www.readbyqxmd.com/read/29122890/microrna-30c-reduces-plasma-cholesterol-in-homozygous-familial-hypercholesterolemic-and-type-2-diabetic-mouse-models
#1
Sara Irani, Jahangir Iqbal, W James Antoni, Laraib Ijaz, M Mahmood Hussain
High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein production; however, this is associated with steatosis. We previously showed that microRNA-30c (miR-30c) lowers diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe-/- mice. Here, we tested miR-30c effect on plasma lipids, transaminases and hepatic lipids in different mouse models. Hepatic delivery of miR-30c to chow fed leptin deficient (ob/ob) and leptin receptor deficient (db/db) hypercholesterolemic and hyperglycemic mice reduced cholesterol in total plasma and VLDL/LDL by ~28% and ~25%, respectively, without affecting triglyceride and glucose levels...
November 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29121499/atorvastatin-accelerates-clearance-of-lipoprotein-remnants-generated-by-activated-brown-fat-to-further-reduce-hypercholesterolemia-and-atherosclerosis
#2
Geerte Hoeke, Yanan Wang, Andrea D van Dam, Isabel M Mol, Eveline Gart, Henk G Klop, Susan M van den Berg, Elsbet H Pieterman, Hans M G Princen, Albert K Groen, Patrick C N Rensen, Jimmy F P Berbée, Mariëtte R Boon
BACKGROUND AND AIMS: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. METHODS: APOE*3-Leiden...
October 26, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29107848/treated-hypothyroidism-is-associated-with-cerebrovascular-disease-but-not-alzheimer-s-disease-pathology-in-older-adults
#3
Willa D Brenowitz, Fang Han, Walter A Kukull, Peter T Nelson
Thyroid hormone disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common manifestation of thyroid disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer's Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2146 without known thyroid disease; hypothyroidism was associated with severe atherosclerosis (odds ratio: 1...
November 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29096854/lectin-like-oxidized-low-density-lipoprotein-receptor-1-promotes-endothelial-dysfunction-in-ldl-receptor-knockout-background
#4
Anja Hofmann, Coy Brunssen, David M Poitz, Heike Langbein, Ruth H Strasser, Thomas Henle, Ursula Ravens, Henning Morawietz
OBJECTIVE: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for oxidized LDL in endothelial cells. LOX-1 is highly expressed in atherosclerotic plaques. The impact of LOX-1 on development of endothelial dysfunction in large vessels in absence or presence of atherosclerosis-prone conditions has not been studied to date. METHODS: Mice with endothelial cell-specific LOX-1 overexpression (bLOX-1tg) were analyzed. Wild-type (WT) mice served as controls...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29068233/subclinical-target-organ-damage-in-subjects-with-different-components-of-metabolic-syndrome
#5
Oxana P Rotar, Maria A Boyarinova, Ekaterina V Moguchaia, Ekaterina P Kolesova, Anastasya M Erina, Vladislav N Solntsev, Alexandra O Konradi, Eugene V Shlyakhto
BACKGROUND: To assess the association of metabolic syndrome (MS) and its components with target organ damage in a follow-up study of relatively healthy bank employers. METHODS: Out of 1600 random samples of office workers in Saint Petersburg (Russia), a group of 383 participants with at least one component of MS and without cardiovascular complications was selected (mean age 46.6 ± 9.0 years, 214 females (64.6%)). Follow-up visit was performed in 331 subjects...
October 25, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28987749/different-manifestation-of-irradiation-induced-coronary-artery-disease-detected-with-coronary-computed-tomography-compared-with-matched-non-irradiated-controls
#6
Alexander R van Rosendael, Laurien A Daniëls, Aukelien C Dimitriu-Leen, Jeff M Smit, Philippe J van Rosendael, Martin J Schalij, Jeroen J Bax, Arthur J H A Scholte
BACKGROUND AND PURPOSE: Patients who received chest irradiation for treatment of a malignancy are at increased risk for the development of coronary artery atherosclerosis. Little is known about the anatomical coronary artery plaque characteristics of irradiation induced coronary artery disease (CAD). This study aimed to evaluate potential differences in the presence, extent, severity, composition and location of CAD in patients treated with mediastinal irradiation compared with non-irradiated controls matched on age, gender and cardiovascular risk factors...
October 4, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28963918/comprehensive-lipid-and-metabolite-profiling-of-children-with-and-without-familial-hypercholesterolemia-a-cross-sectional-study
#7
Jacob J Christensen, Stine M Ulven, Kjetil Retterstøl, Ingunn Narverud, Martin P Bogsrud, Tore Henriksen, Jens Bollerslev, Bente Halvorsen, Pål Aukrust, Kirsten B Holven
BACKGROUND AND AIMS: Individuals with familial hypercholesterolemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C), accelerated atherosclerosis, and premature cardiovascular disease. Whereas children with lifestyle-induced dyslipidemias often present with complex lipid abnormalities, children with FH have isolated hypercholesterolemia. However, to the best of our knowledge, a comprehensive profiling of FH children is lacking. Therefore, we aimed to characterize the lipid-related and metabolic alterations associated with elevated LDL-C in children with FH and healthy children...
November 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28910310/gugulipid-causes-hypercholesterolemia-leading-to-endothelial-dysfunction-increased-atherosclerosis-and-premature-death-by-ischemic-heart-disease-in-male-mice
#8
Andrea Leiva, Susana Contreras-Duarte, Ludwig Amigo, Esteban Sepúlveda, Mauricio Boric, Verónica Quiñones, Dolores Busso, Attilio Rigotti
For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI), a high-density lipoprotein (HDL) receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28815569/glucose-dependent-leucocyte-activation-in-familial-hypercholesterolemia
#9
Natasja Koks, Marijke A de Vries, Erwin Birnie, Arash Alipour, Manuel Castro Cabezas
BACKGROUND: Leucocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leucocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidaemia. Our study aim was to evaluate the effect of post-OGTT hyperglycaemia on leucocyte activation in patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28655430/deuterium-reinforced-polyunsaturated-fatty-acids-protect-against-atherosclerosis-by-lowering-lipid-peroxidation-and-hypercholesterolemia
#10
Jimmy F P Berbée, Isabel M Mol, Ginger L Milne, Erik Pollock, Geerte Hoeke, Dieter Lütjohann, Claudia Monaco, Patrick C N Rensen, Lex H T van der Ploeg, Mikhail S Shchepinov
BACKGROUND AND AIMS: Oxidative modification of lipoproteins is a crucial step in atherosclerosis development. Isotopic-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to reactive oxygen species-initiated chain reaction of lipid peroxidation than regular hydrogenated (H-)PUFAs. We aimed at investigating the effect of D-PUFA treatment on lipid peroxidation, hypercholesterolemia and atherosclerosis development. METHODS: Transgenic APOE*3-Leiden...
June 21, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28640873/healthy-aging-of-the-left-ventricle-in-relationship-to-cardiovascular-risk-factors-the-multi-ethnic-study-of-atherosclerosis-mesa
#11
Chia-Ying Liu, Shenghan Lai, Nadine Kawel-Boehm, Harjit Chahal, Bharath Ambale-Venkatesh, Joao A C Lima, David A Bluemke
BACKGROUND: Understanding the relationship of cardiovascular structure and function to age is confounded by the high prevalence of traditional risk factors in the United States. The purpose of the study is to compare left ventricular (LV) and aortic structural, and functional parameters in individuals with and without traditional risk factors in a population-based cohort. METHODS AND RESULTS: 3015 study participants (48% men, age 55-94, mean 69.01±9.17 years) in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent cardiovascular magnetic resonance (CMR) imaging from 2010-2012...
2017: PloS One
https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#12
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. METHODS: We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
July 13, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28567091/effect-of-rosuvastatin-on-bovine-pericardial-aortic-tissue-valve-calcification-in-a-rat-subdermal-implantation-model
#13
Seung Hyun Lee, Dae-Hyun Kim, Young-Nam Youn, Sak Lee, Hyun Chel Joo, Byung Chul Chang, Kyung-Jong Yoo
BACKGROUND AND OBJECTIVES: There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of this study was to examine the effects of statin treatment on calcification in bovine pericardial tissue valves. MATERIALS AND METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups according to hypercholesterolemia induction and statin intake (Group 1, n=10: normal diet without statin treatment, Group 2, n=10: normal diet with statin treatment, Group 3, n=10: high fat diet without statin treatment, Group 4, n=10: high fat diet with statin treatment)...
May 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#14
REVIEW
Nathan D Wong, Paul D Rosenblit, Robert S Greenfield
In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries...
April 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28504688/accelerated-atherosclerosis-development-in-c57bl6-mice-by-overexpressing-aav-mediated-pcsk9-and-partial-carotid-ligation
#15
Sandeep Kumar, Dong-Won Kang, Amir Rezvan, Hanjoong Jo
Studying the role of a particular gene in atherosclerosis typically requires a time-consuming and often difficult process of generating double knockouts or transgenics on ApoE(-/-) or LDL receptor (LDLR)(-/-) background. Recently, it was reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6 wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial carotid ligation model is used to rapidly develop atherosclerosis by inducing disturbed flow in the left common carotid artery within 2 weeks in ApoE(-/-) or LDLR(-/-) mice...
August 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28502908/chronic-administration-of-antioxidant-resin-from-virola-oleifera-attenuates-atherogenesis-in-ldlr-mice
#16
Paola Nogueira Coutinho, Beatriz Peters Pereira, Ana Claudia Hertel Pereira, Marcella Leite Porto, Arícia Leone Evangelista Monteiro de Assis, Afrânio Côgo Destefani, Silvana Santos Meyrelles, Elisardo Corral Vasquez, Breno Valentim Nogueira, Tadeu Uggere de Andrade, Denise Coutinho Endringer, Marcio Fronza, Thiago Melo Costa Pereira
ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A. C. Smith, Myristicaceae has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and our previous data indicated the antioxidant properties in other oxidative stress-related models. However, its effects on atherosclerosis (AT) are not yet investigated. AIMS OF THE STUDY: To evaluate the influence of resin from Virola oleifera (RV) on progression of AT in LDLr(-/-) mice...
July 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28456681/early-coronary-calcifications-are-related-to-cholesterol-burden-in-heterozygous-familial-hypercholesterolemia
#17
Antonio Gallo, Philippe Giral, Alain Carrié, Valérie Carreau, Sophie Béliard, Randa Bittar, Marianna Maranghi, Marcello Arca, Philippe Cluzel, Alban Redheuil, Eric Bruckert, David Rosenbaum
BACKGROUND: The identification of high-risk patients with heterozygous familial hypercholesterolemia (HeFH) that may benefit from early treatment is challenging. Coronary Artery Calcification (CAC) score accounts for coronary atherosclerotic burden. It has proven its accuracy in cardiovascular risk assessment in the general population but data in HeFH are lacking. OBJECTIVE: The aim of our study was to assess CAC prevalence and its relationship with lifelong cholesterol exposure, calculated by total cholesterol burden (TCB) in patients with HeFH...
April 4, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28420489/mast-cells-emerge-as-mediators-of-atherosclerosis-special-emphasis-on-il-37-inhibition
#18
REVIEW
Pio Conti, Gianfranco Lessiani, Spyridon K Kritas, Gianpaolo Ronconi, Aessandro Caraffa, Theoharis C Theoharides
In atherosclerosis lipoproteins stimulate the innate immune response, leading to the release of inflammatory cytokines and chemokines. Hypercholesterolemia may activate the synthesis and release of inflammatory cytokines such as IL-1, which induces TNF release in mast cells (MCs). IL-1 and IL-1 family members orchestrate a broadening list of inflammatory diseases, including atherosclerosis. MCs are implicated in the pathophysiology of several diseases including allergy and inflammation. Activated MCs, located perivascularly, contribute to inflammation in atherosclerosis by producing inflammatory cytokines...
June 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28368771/investigational-therapies-for-hypercholesterolemia
#19
REVIEW
Gerald H Tomkin, Daphne Owens
Cardiovascular morbidity and mortality are of increasing concern, not only to patients but also to the health care profession and service providers. The preventative benefit of treatment of dyslipidaemia is unquestioned but there is a large, so far unmet need to improve clinical outcome. There are exciting new discoveries of targets that may translate into improved clinical outcome. Areas covered: This review highlights some new pathways in cholesterol and triglyceride metabolism and examines new targets, new drugs and new molecules...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28321823/cardiovascular-disease-and-resuscitated-septic-shock-lead-to-the-downregulation-of-the-h2s-producing-enzyme-cystathionine-%C3%AE-lyase-in-the-porcine-coronary-artery
#20
Tamara Merz, Tatjana Stenzel, Benedikt Nußbaum, Martin Wepler, Csaba Szabo, Rui Wang, Peter Radermacher, Oscar McCook
BACKGROUND: Downregulation of the hydrogen sulfide (H2S)-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and/or 3-mercaptopyruvate sulfurtransferase (3-MST) is associated with chronic cardiovascular pathologies. Nevertheless, equivocal data are available on both the expression and function of these enzymes in coronary arteries (CA). We recently reported that atherosclerotic pigs subjected to sepsis developed impaired cardiac function, which coincided with decreased myocardial CSE expression and increased nitrotyrosine formation...
December 2017: Intensive Care Medicine Experimental
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