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Alexis Stamatikos, Nagadhara Dronadula, Philip Ng, Donna Palmer, Ethan Knight, Bradley Wacker, Chongren Tang, Francis Kim, David A Dichek
Atherosclerosis, a disease of blood vessels, is driven by cholesterol accumulation and inflammation. Gene therapy that removes cholesterol from blood vessels and decreases inflammation is a promising approach for prevention and treatment of atherosclerosis. In previous work, we reported that helper-dependent adenoviral (HDAd) overexpression of apolipoprotein A-I (apoAI) in endothelial cells (EC) increases cholesterol efflux in vitro and reduces atherosclerosis in vivo. However, the effect of HDAdApoAI on atherosclerosis is partial...
August 4, 2018: Human Gene Therapy
Xinyun Huang, Yuan Lv, Panpan He, Zongbao Wang, Fang Xiong, Linhao He, Xilong Zheng, Dawei Zhang, Qi Cao, Chaoke Tang
Cholesterol is one of the major components of biological membranes and has an important function in osteoclast formation and survival. It has been reported that high-density lipoprotein (HDL) promotes cholesterol efflux from osteoclasts and induces their apoptosis, but the underlying mechanisms are unclear. In this study, we investigated how HDL promotes osteoclast cholesterol efflux and explored its effect on osteoclast formation and survival. Our results showed that the maximum diameter and fusion index of osteoclasts were decreased, while the ratios of osteoclasts with pyknotic nuclei were increased when cells were treated with HDL (600 ng/ml), as revealed by tartrate-resistant acid phosphatase-positive staining and microscopy assay...
July 27, 2018: Acta Biochimica et Biophysica Sinica
Lin Chen, Minzeng Sun, Hui Liu, Lihui Ma, Tiansong Wang, Peiqiong Li, Mingqin Lin, Haifeng Lin, Penghuan Chang, Yueli Liu
BACKGROUND: Apolipoprotein CIII (apoCIII) is an independent risk for coronary heart disease (CHD). In this study, we investigated the associations among plasma apoCIII, hs-CRP and TNF-α levels and their roles in the clinical features of CHD in the Li and Han ethnic groups in China. METHODS: A cohort of 474 participants was recruited (238 atherosclerotic patients and 236 healthy controls) from the Li and Han ethnic groups. Blood samples were obtained to evaluate apoCIII, TNF-α, hs-CRP and lipid profiles...
July 27, 2018: Lipids in Health and Disease
Gaya W Katulanda, Harsha A Dissanayake, Prasad Katulanda, David R Matthews, Brian Shine
AIMS: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD). Apolipoproteins are emerging as powerful predictors of CVD. We aimed to study associations of metabolic syndrome and apoB, apoAI, apoB/AI ratio in young Sri Lankans with type 2 diabetes. MATERIALS & METHODS: Blood samples were available from 690 patients with type 2 diabetes in Sri Lanka Young Diabetes Study, and were analysed for apoB, apoAI, total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG) and glycated haemoglobin (HbA1c )...
July 17, 2018: Diabetes & Metabolic Syndrome
Narin Nasiroglu Imga, Canan Topcuoglu, Dilek Berker, Turan Turhan
BACKGROUND: Adrenal incidentalomas (AIs), particularly subclinical hypercortisolism (SH), are related to an increased risk of atherosclerosis. The anti-oxidative enzyme paraoxonase-1 (PON1) and the acute phase reactant serum amyloid A (SAA) are transported by highdensity lipoprotein and reciprocally regulated in acute inflammatory response. Our aim was to investigate serum SAA, PON1, and apolipoprotein levels as indicators of subclinical atherosclerosis in patients with nonfunctioning AI (NFAI) and SH...
July 18, 2018: Archives of Medical Research
Dipu Bharali, Basu Dev Banerjee, Mausumi Bharadwaj, Syed Akhtar Husain, Premashis Kar
Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study...
April 2018: Indian Journal of Medical Research
Dimitris Theofilatos, Panagiotis Fotakis, Efi Valanti, Despina Sanoudou, Vassilis Zannis, Dimitris Kardassis
BACKGROUND: High Density Lipoprotein (HDL) and its main protein component, apolipoprotein A-I (apoA-I) have numerous atheroprotective functions on various tissues including the endothelium. Therapies based on reconstituted HDL containing apoA-I (rHDL-apoA-I) have been used successfully in patients with acute coronary syndrome, peripheral vascular disease or diabetes but very little is known about the genomic effects of rHDL-apoA-I and how they could contribute to atheroprotection. OBJECTIVE: The present study aimed to understand the endothelial signaling pathways and the genes that may contribute to rHDL-apoA-I-mediated atheroprotection...
June 18, 2018: Metabolism: Clinical and Experimental
Lukasz Szternel, Magdalena Krintus, Katarzyna Bergmann, Tadeusz Derezinski, Grazyna Sypniewska
OBJECTIVE: Despite the common use of non-fasting measurements for lipid profile in children it remains unclear as to the extent non-fasting conditions have on laboratory results of lipids measurements. We aimed to assess the impact of non-fasting lipid profile on the occurrence of dyslipidemia in children. MATERIALS AND METHODS: Basic lipid profile including: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), as well as small, dense-LDL-C (sd-LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)], were measured in 289 presumably healthy children aged 9-11 in both fasting and non-fasting condition...
2018: PloS One
Jia Cao, Yanyong Xu, Feifei Li, Liang Shang, Daping Fan, Hong Yu
BACKGROUND: Scavenger receptor class B type I (SR-BI) plays a key role in high density lipoproteins (HDL) metabolism. SR-BI deficiency in mice results in enhanced susceptibility to atherosclerosis with abnormal large, cholesterol enriched, and functional impaired HDL. This study was to characterize the protein markers of dysfunctional HDL in SR-BI deficient (SR-BI-/- ) mice and to test if the defective of HDL might be affected by probucol treatment. METHODS: Shotgun proteomics and 2-D gel electrophoresis were performed to examine the profile of HDL protein and distribution of HDL particles isolated from SR-BI-/- mice...
June 7, 2018: Journal of Translational Medicine
Massimiliano Ruscica, Sara Simonelli, Margherita Botta, Alice Ossoli, Maria Giovanna Lupo, Paolo Magni, Alberto Corsini, Marcello Arca, Livia Pisciotta, Fabrizio Veglia, Guido Franceschini, Nicola Ferri, Laura Calabresi
Proprotein convertase subtilisin/kexin 9 (PCSK9), a protein regulating the number of cell-surface LDL receptors (LDLR), circulates partially associated to plasma lipoproteins. How this interaction alters PCSK9 plasma levels is still unclear. In the present study, we took advantage of the availability of a large cohort of carriers of genetic HDL disorders to evaluate how HDL defects affect plasma PCSK9 levels and its distribution among lipoproteins. Plasma PCSK9 concentrations were determined by ELISA in carriers of mutations in LCAT, ABCA1, or APOAI genes, and lipoprotein distribution was analyzed by FPLC...
September 2018: Biochimica et Biophysica Acta
Wendy A M Blom, Wieneke P Koppenol, Harry Hiemstra, Tatjana Stojakovic, Hubert Scharnagl, Elke A Trautwein
PURPOSE: The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread. METHODS: This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3...
May 3, 2018: European Journal of Nutrition
Qianjin Zhang, Jine Hu, Yichuan Hu, Ying Ding, Jingjing Zhu, Changjiang Zhuang
AIMS: Prognostic significance of apolipoproteins in diabetic retinopathy risk has not been well investigated. The aim of this study was to reveal the relationship between the risk of diabetic retinopathy and the levels of several apolipoproteins and their ratios in a 10-year prospective cohort. METHODS: A total of 1023 diabetic patients without retinopathy were selected from a 10-year hospital-based diabetic cohort. In this cohort, all subjects had type 2 diabetes...
July 2018: Acta Diabetologica
Elżbieta Kimak, Bartosz Zięba, Dariusz Duma, Janusz Solski
BACKGROUND: Myeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined...
April 4, 2018: Lipids in Health and Disease
Nicholas J Viney, Calvin Yeang, Xiaohong Yang, Shuting Xia, Joseph L Witztum, Sotirios Tsimikas
BACKGROUND: The laboratory measurement of "low-density lipoprotein cholesterol (LDL-C)" includes the cholesterol content of lipoprotein(a) (Lp(a)-C). OBJECTIVE: To estimate the "true" LDL-C in relation to changes in apolipoprotein B-100 (apoB-100) and assess changes in proprotein convertase subtilisin/kexin 9 (PCSK9) levels in patients with elevated Lp(a) treated with IONIS-APO(a)Rx. METHODS: A pooled placebo group (n = 29), and cohort A (n = 24, baseline Lp(a) 50-175 mg/dL) and cohort B (n = 8, baseline Lp(a) > 175 mg/dL) treated with IONIS-APO(a)Rx were studied...
May 2018: Journal of Clinical Lipidology
M John Chapman, Alexina Orsoni, Paul Robillard, Patrice Therond, Philippe Giral
BACKGROUND: Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. OBJECTIVE: We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. METHODS: Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days...
May 2018: Journal of Clinical Lipidology
Hui Chang, Jia-Wang Wei, Kai Chen, Shu Zhang, Fei Han, Li-Xia Lu, Wei-Wei Xiao, Yuan-Hong Gao
Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid)...
2018: Journal of Cancer
Dalia E Gaddis, Lindsey E Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M Taylor, Coleen A McNamara, Mitchell Kronenberg, Shane Crotty, Michael J Thomas, Mary G Sorci-Thomas, Catherine C Hedrick
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα...
March 15, 2018: Nature Communications
Satomi Minato, Kaori Kitaoka, Mika Takeuchi, Ayaka Tsuboi, Miki Kurata, Shigehiro Tanaka, Tsutomu Kazumi, Keisuke Fukuo
Objective: We test the hypothesis that aspartate aminotransferase (AST) may be associated inversely with serum triglycerides (TG) and positively with high density lipoprotein (HDL) cholesterol in young athletes because athletes have larger amounts of muscle mass. Research design and methods: Pearson's correlation coefficients were calculated between serum AST and alanine aminotransferase (ALT) and body composition identified by dual-energy X-ray absorptiometry, markers of insulin resistance, serum lipids, lipoproteins, apolipoproteins, adiponectin and leptin in 174 female collegiate athletes (18-22 years)...
2018: BMJ Open Diabetes Research & Care
Zhao Dong, Haozhe Shi, Mingming Zhao, Xin Zhang, Wei Huang, Yuhui Wang, Lemin Zheng, Xunde Xian, George Liu
OBJECTIVE: Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis...
June 2018: Metabolism: Clinical and Experimental
Adriana Pané, Sabina Ruiz, Aida Orois, Daniel Martínez, Mattia Squarcia, Lydia Sastre, Pablo Ruiz, Joan Caballería, Mireia Mora, Felicia A Hanzu, Irene Halperin
Several mutations in the gene encoding apolipoprotein AI (apoAI) have been described as a cause of familial amyloidosis. Individuals with apoAI-derived (AApoAI) amyloidosis frequently manifest with liver, kidney, laryngeal, skin and myocardial involvement. Although primary hypogonadism (PH) is considered almost pathognomonic of this disease, until now, primary adrenal insufficiency (PAI) has not been described as a common clinical feature. Here, we report the first kindred with AApoAI amyloidosis in which PAI is well-documented...
February 15, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
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