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hypercholesterolemia without atherosclerosis

A Mattina, D Rosenbaum, R Bittar, D Bonnefont-Rousselot, D Noto, M Averna, E Bruckert, P Giral
BACKGROUND AND AIM: Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH...
February 2, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Hiroko Watase, Jie Sun, Daniel S Hippe, Niranjan Balu, Feiyu Li, Xihai Zhao, Venkatesh Mani, Zahi A Fayad, Valentin Fuster, Thomas S Hatsukami, Chun Yuan
OBJECTIVE: Early atherosclerosis is often undetected due in part to compensatory enlargement of the outer wall, termed positive remodeling. Variations in hemodynamic conditions and clinical factors influence the patterns of remodeling. The carotid artery provides an opportunity to examine these variations because of the unique geometry of the carotid bulb. This study aimed to determine differences in remodeling of the common, internal, and bifurcation segments of the carotid using magnetic resonance imaging...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Jan-Willem Balder, Antoine Rimbert, Xiang Zhang, Martijn Viel, Roan Kanninga, Freerk van Dijk, Peter Lansberg, Richard Sinke, Jan Albert Kuivenhoven
BACKGROUND: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women. METHODS: We randomly selected for every year of age 8 women with LDL-C ≤1st percentile (≤50 mg/dL) and 8 women with LDL-C ≥99th percentile (≥186 mg/dL) from 28 000 female participants aged between 25 to 40 years of a population-based cohort study...
February 20, 2018: Circulation
Debapriya Basu, Yunying Hu, Lesley-Ann Huggins, Adam E Mullick, Mark J Graham, Tomasz Wietecha, Shelley Barnhart, Allison Mogul, Katharina Pfeiffer, Andreas Zirlik, Edward A Fisher, Karin E Bornfeldt, Florian Willecke, Ira J Goldberg
RATIONALE: Animal models have been used to explore factors that regulate atherosclerosis. More recently, they have been used to study the factors that promote loss of macrophages and reduction in lesion size after lowering of plasma cholesterol levels. However, current animal models of atherosclerosis regression require challenging surgeries, time-consuming breeding strategies, and methods that block liver lipoprotein secretion. OBJECTIVE: We sought to develop a more direct or time-effective method to create and then reverse hypercholesterolemia and atherosclerosis via transient knockdown of the hepatic LDLR (low-density lipoprotein receptor) followed by its rapid restoration...
February 16, 2018: Circulation Research
Anastasia Garoufi, Antonios Marmarinos, Venetia-Maria Vraila, Stamatina Dimou, Athanasia Pagoni, Styliani Vorre, Irene Paraskakis, Dimitrios Gourgiotis
BACKGROUND: The oxidative modification of LDL (oxLDL) appears to play a key role in the early developmental stages of atherosclerosis. Increased serum antibodies against the oxLDL (anti-oxLDL antibodies) have been found in adults with atherosclerotic diseases, as well as in healthy ones. However, the clinical significance and its precise role, atherogenic or atheroprotective, have not been yet clarified. This study aims in evaluating anti-oxLDL antibodies in healthy children and adolescents with- and without hypercholesterolemia...
January 3, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
Lorena Airaghi, Mario Rango, Diletta Maira, Valentina Barbieri, Luca Valenti, Rosa Lombardi, Pietro Biondetti, Silvia Fargion, Anna Ludovica Fracanzani
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease. METHODS: In this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity). RESULTS: The results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i...
January 2018: Atherosclerosis
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
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...
December 2017: Atherosclerosis
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...
February 2018: Neurobiology of Aging
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
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
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 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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
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
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
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
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
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
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
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
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