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https://www.readbyqxmd.com/read/28207870/impaired-hdl2-mediated-cholesterol-efflux-is-associated-with-metabolic-syndrome-in-families-with-early-onset-coronary-heart-disease-and-low-hdl-cholesterol-level
#1
Timo Paavola, Sanna Kuusisto, Matti Jauhiainen, Sakari Kakko, Tiia Kangas-Kontio, Jari Metso, Pasi Soininen, Mika Ala-Korpela, Risto Bloigu, Minna L Hannuksela, Markku J Savolainen, Tuire Salonurmi
OBJECTIVE: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. METHODS: HDL subfractions were isolated from plasma by sequential ultracentrifugation...
2017: PloS One
https://www.readbyqxmd.com/read/28205166/assaying-low-density-lipoprotein-ldl-uptake-into-cells
#2
Anke Loregger, Jessica K Nelson, Noam Zelcer
Determination of LDL particle uptake into cells is a valuable technique in the field of cholesterol metabolism. This allows assessment of LDL uptake capacity in different adherent and non-adherent cells types, as well as the effect of cellular, genetic, or pharmacological perturbations on this process. Here, we detail a general procedure that describes the production of fluorescently-labeled LDL particles and quantitative and non-quantitative assays for determining cellular LDL uptake.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28204818/reactive-oxygen-species-mediate-angiotensin-ii-induced-transcytosis-of-low-density-lipoprotein-across-endothelial-cells
#3
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)...
February 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202546/identification-of-a-novel-series-of-anti-inflammatory-and-anti-oxidative-phospholipid-oxidation-products-containing-cyclopentenone-moiety-in-vitro-and-in-vivo-implication-in-atherosclerosis
#4
Jianhong Lu, Shuyuan Guo, Xinli Xue, Qun Chen, Jing Ge, Yujuan Zhuo, Huiqin Zhong, Buxing Chen, Mingming Zhao, Wei Han, Takashi Suzuki, Mingjiang Zhu, Lin Xia, Claus Schneider, Timothy S Blackwell, Ned A Porter, Lemin Zheng, Sotirios Tsimikas, Huiyong Yin
Oxidative stress and inflammation are two major contributing factors to atherosclerosis, a leading cause for cardiovascular diseases (CVDs). Oxidation of phospholipids on the surface of low density lipoprotein (LDL) particles generated under oxidative stress has been associated with the progression of atherosclerosis but the underlying molecular mechanisms remain poorly defined. We identified a novel series of oxidation products containing cyclopentenone moiety, termed deoxy-A2/J2-isoprostanes-phosphocholine (deoxy-A2/J2-IsoP-PC), from 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) in vivo using mass spectrometry and by comparison to a chemically synthesized standard...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199736/impact-of-hormonal-contraception-and-weight-loss-on-hdl-c-efflux-and-lipoprotein-particles-in-women-with-polycystic-ovary-syndrome
#5
Anuja Dokras, Martin Playford, Penny M Kris-Etherton, Allen R Kunselman, Christy M Stetter, Nancy I Williams, Carol L Gnatuk, Stephanie J Estes, David B Sarwer, Kelly C Allison, Christos Coutifaris, Nehal Mehta, Richard S Legro
OBJECTIVE: To study the effects of oral contraceptive pills (OCP), the first line treatment for PCOS, on HDL-C function (reverse cholesterol efflux capacity) and lipoprotein particles measured by NMR spectroscopy. DESIGN: Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive lifestyle modification) or Combined (OCP+Lifestyle) treatment for 16 weeks. PATIENTS: 87 overweight/obese women with PCOS at two academic centers...
February 15, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28194698/pathophysiology-and-treatment-of-atherosclerosis-current-view-and-future-perspective-on-lipoprotein-modification-treatment
#6
REVIEW
S C Bergheanu, M C Bodde, J W Jukema
Recent years have brought a significant amount of new results in the field of atherosclerosis. A better understanding of the role of different lipoprotein particles in the formation of atherosclerotic plaques is now possible. Recent cardiovascular clinical trials have also shed more light upon the efficacy and safety of novel compounds targeting the main pathways of atherosclerosis and its cardiovascular complications.In this review, we first provide a background consisting of the current understanding of the pathophysiology and treatment of atherosclerotic disease, followed by our future perspectives on several novel classes of drugs that target atherosclerosis...
February 13, 2017: Netherlands Heart Journal
https://www.readbyqxmd.com/read/28188431/lipoprotein-a-and-its-role-in-inflammation-atherosclerosis-and-malignancies
#7
Evelyn Orsó, Gerd Schmitz
Lipoprotein (a) (Lp(a)) is a modified low-density lipoprotein (LDL) particle with an additional specific apolipoprotein (a), covalently attached to apolipoprotein B‑100 of LDL by a single thioester bond. Increased plasma Lp(a) level is a genetically determined, independent, causal risk factor for cardiovascular disease.The precise quantification of Lp(a) in plasma is still hampered by mass-sensitive assays, large particle variation, poor standardization and lack of assay comparability.The physiological functions of Lp(a) include wound healing, promoting tissue repair and vascular remodeling...
February 10, 2017: Clinical Research in Cardiology Supplements
https://www.readbyqxmd.com/read/28187765/does-a-lack-of-physical-activity-explain-the-rheumatoid-arthritis-lipid-profile
#8
Hiba AbouAssi, Margery A Connelly, Lori A Bateman, K Noelle Tune, Janet L Huebner, Virginia B Kraus, Deborah A Winegar, James D Otvos, William E Kraus, Kim M Huffman
BACKGROUND: In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile...
February 10, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28185214/prevention-of-cardiovascular-complications-in-patients-with-lp-a-hyperlipoproteinemia-and-progressive-cardiovascular-disease-by-long-term-lipoprotein-apheresis-according-to-german-national-guidelines
#9
Reinhard Klingel, Andreas Heibges, Cordula Fassbender
Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60-70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008...
February 9, 2017: Clinical Research in Cardiology Supplements
https://www.readbyqxmd.com/read/28183443/improvement-of-the-omega-3-index-of-healthy-subjects-does-not-alter-the-effects-of-dietary-saturated-fats-or-n-6pufa-on-ldl-profiles
#10
Cintia B Dias, Núria Amigó, Lisa G Wood, Roger Mallol, Xavier Correig, Manohar L Garg
BACKGROUND AND AIMS: Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. METHODS: In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28174174/discordance-between-circulating-atherogenic-cholesterol-mass-and-lipoprotein-particle-concentration-in-relation-to-future-coronary-events-in-women
#11
Patrick R Lawler, Akintunde O Akinkuolie, Paul M Ridker, Allan D Sniderman, Julie E Buring, Robert J Glynn, Daniel I Chasman, Samia Mora
BACKGROUND: It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass (non-HDL cholesterol [nonHDLc]) or particle concentration (apolipoprotein B[apo B] and LDL particle concentration [LDLp]) more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant. METHODS: Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models...
February 7, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28166253/effects-of-a-very-high-saturated-fat-diet-on-ldl-particles-in-adults-with-atherogenic-dyslipidemia-a-randomized-controlled-trial
#12
Sally Chiu, Paul T Williams, Ronald M Krauss
BACKGROUND: Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response. OBJECTIVE: The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B)...
2017: PloS One
https://www.readbyqxmd.com/read/28164576/oxidized-low-density-lipoprotein-ox-ldl-to-ldl-ratio-ox-ldl-ldl-and-ox-ldl-to-high-density-lipoprotein-ratio-ox-ldl-hdl
#13
Mahtab Motamed, Arash A Nargesi, Behnam Heidari, Hossein Mirmiranpour, Alireza Esteghamati, Manouchehr Nakhjavani
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) plays a principal role in diabetes complications, though ox-LDL concentrations and its functions are dependents of other oxidative and anti-oxidative particles. The oxLDL to low-density lipoprotein ratio (ox-LDL/LDL) and ox-LDL to high-density lipoprotein ratio (ox-LDL/HDL) as new lipid biomarkers may serve as a good estimation of oxidation and anti-oxidation in type 2 diabetes mellitus. The aim of this study was first to examine ox-LDL/LDL and ox-LDL/HDL levels in patients with type 2 diabetes mellitus compared to a control group and evaluate their diagnostic accuracies, and, second, to investigate the correlation of these two ratios with triglyceride and HDL levels...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28137217/anti-pcsk9-antibodies-a-new-era-in-the-treatment-of-dyslipidemia
#14
Joel Schmitz, Ioanna Gouni-Berthold
The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomal degradation. This results in decreased numbers of LDLR available on the cell surface to bind LDL particles and remove them from the circulation which in turn leads to an increase in circulating LDL-cholesterol (LDL-C) concentrations. Since the role PCSK9 plays in LDL-C metabolism has been discovered in 2003 there have been major efforts in finding efficient and safe methods to inhibit it...
January 30, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28128058/apolipoprotein-a-antisense-oligonucleotides-a-new-treatment-option-for-lowering-elevated-lipoprotein-a
#15
Julia Schreml, Ioanna Gouni-Berthold
BACKGROUND: Lipoprotein(a) [Lp(a)] is a particle similar to LDL that contains an additional protein called apolipoprotein(a) [apo(a)]. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) may be causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). While the risk association between Lp(a) concentrations and CVD is weak it seems to be continuous in shape and without an obvious threshold for Lp(a) levels. METHODS: Circulating concentrations of Lp(a) are genetically determined and desirable levels are < 50 mg/dl...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28125987/method-for-estimating-high-sdldl-c-by-measuring-triglyceride-and-apolipoprotein-b-levels
#16
Toshiyuki Hayashi, Shinji Koba, Yasuki Ito, Tsutomu Hirano
BACKGROUND: We previously developed an assay to directly measure small dense (sd) low-density lipoprotein cholesterol (LDL-C) levels, which is not widely used in general clinical practice. Therefore, we propose a simpler method, "LDL window," that uses conventional methods for estimating high sdLDL-C levels. METHODS: We analyzed our previous studies (2006-2008) on healthy subjects and patients with type 2 diabetes and coronary artery disease (CAD). The sdLDL-C level was measured using the precipitation method, and LDL size was determined using gradient gel electrophoresis...
January 26, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28120723/multiple-modified-low-density-lipoprotein-as-atherogenic-factor-of-patients-blood-development-of-therapeutic-approaches-to-reduce-blood-atherogenicity
#17
N G Nikiforov, E R Zakiev, N V Elizova, V N Sukhorukov, A N Orekhov
Generally, atherosclerosis first occurs by the way of accumulation of intracellular and extracellular lipids in the arterial intima. Foam cells, overloaded by lipids, are the essential harbinger of the coronary artery disease. It should be noted that lipids that are usually composed of bulk of the intracellular lipids found in human arterial cells originate from low-density lipoprotein (LDL) circulating in human blood. Nonetheless, many efforts to force cells to accumulate cholesteryl esters under the influence of native LDL have been unsuccessful...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28111237/human-neutrophil-peptide-1-limits-hypercholesterolemia-induced-atherosclerosis-by-increasing-hepatic-ldl-clearance
#18
Nicole Paulin, Yvonne Döring, Sander Kooijman, Xavier Blanchet, Joana R Viola, Renske de Jong, Manuela Mandl, Jeffrey Hendrikse, Maximilian Schiener, Philipp von Hundelshausen, Anja Vogt, Christian Weber, Khalil Bdeir, Susanna M Hofmann, Patrick C N Rensen, Maik Drechsler, Oliver Soehnlein
Increases in plasma LDL-cholesterol have unequivocally been established as a causal risk factor for atherosclerosis. Hence, strategies for lowering of LDL-cholesterol may have immediate therapeutic relevance. Here we study the role of human neutrophil peptide 1 (HNP1) in a mouse model of atherosclerosis and identify its potent atheroprotective effect both upon transgenic overexpression and therapeutic delivery. The effect was found to be due to a reduction of plasma LDL-cholesterol. Mechanistically, HNP1 binds to apolipoproteins enriched in LDL...
January 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28108250/synthesis-of-vorinostat-and-cholesterol-conjugate-to-enhance-the-cancer-cell-uptake-selectivity
#19
Nethrie D Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su
Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108216/the-phenomenon-of-atherosclerosis-reversal-and-regression-lessons-from-animal-models
#20
REVIEW
Dimitry A Chistiakov, Veronika A Myasoedova, Victor V Revin, Alexander N Orekhov, Yuri V Bobryshev
Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications. Lowering of low density lipoprotein (LDL) cholesterol and the activation of reverse cholesterol transport lead to a decline in foam cell content, to the depletion of plaque lipid reservoirs, a decrease in lesional macrophage numbers through the activation of macrophage emigration and, probably, apoptosis, dampening plaque inflammation, and the induction of anti-inflammatory macrophages involved in clearance of the necrotic core and plaque healing...
January 17, 2017: Experimental and Molecular Pathology
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