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L5 lipoprotein

Jiz-Yuh Wang, Chiou-Lian Lai, Ching-Tien Lee, Chen-Yen Lin
There have been striking associations of cardiovascular diseases (e.g., atherosclerosis) and hypercholesterolemia with increased risk of neurodegeneration including Alzheimer's disease (AD). Low-density lipoprotein (LDL), a cardiovascular risk factor, plays a crucial role in AD pathogenesis; further, L5, a human plasma LDL fraction with high electronegativity, may be a factor contributing to AD-type dementia. Although L5 contributing to atherosclerosis progression has been studied, its role in inducing neurodegeneration remains unclear...
August 11, 2017: International Journal of Molecular Sciences
Chiz-Tzung Chang, Ming-Yi Shen, An-Sean Lee, Chun-Cheng Wang, Wei-Yu Chen, Chia-Ming Chang, Kuan-Cheng Chang, Nicole Stancel, Chu-Huang Chen
Electronegative low-density lipoprotein (LDL) has been shown to increase coronary artery disease risk in hemodialysis patients, but its effect on the risk of peripheral artery disease (PAD) remains unclear. We separated plasma LDL from 90 uremia patients undergoing hemodialysis into 5 subfractions (L1-L5) according to charge by using fast-protein liquid chromatography with an anion-exchange column and examined the distribution of L5-the most electronegative LDL subfraction-in total LDL (i.e. L5%). During a 5-year period, we followed up with these patients until the occurrence of ischemic lower-extremity PAD...
July 5, 2017: Scientific Reports
Liang-En Yu, Chiou-Lian Lai, Ching-Tien Lee, Jiz-Yuh Wang
Atherogenic risk factors, such as hypercholesterolemia, are associated with increased risk of neurodegeneration, especially Alzheimer's dementia. Human plasma electronegative low-density lipoprotein [LDL(-)], especially L5, may serve as an important contributing factor. L5 promoting an inflammatory action in atherosclerosis has been extensively studied. However, the role of L5 in inducing neuroinflammation remains unknown. Here, we examined the impact of L5 on immune activation and cell viability in cultured BV-2 microglia...
July 2017: Journal of Neurochemistry
C González-Álvarez, N Ramos-Ibáñez, J Azprioz-Leehan, L Ortiz-Hernández
BACKGROUND/OBJECTIVE: Few studies in Latin American paediatric populations have differentiated fat deposits in specific areas, such as intra-abdominal fat (IAF) and subcutaneous abdominal fat (SAF). Research in diverse populations is needed, as patterns of fat accumulation vary by ethnicity. The aim of this study was to determine whether IAF and/or SAF are related to cardiometabolic risk factors, independent of total body fat (TBF), in a group of Mexican schoolchildren. SUBJECTS/METHODS: A cross-sectional study was conducted in Mexico City with 94 children aged between 5 and 11 years...
April 5, 2017: European Journal of Clinical Nutrition
Sumeyya Akyol, Jonathan Lu, Omer Akyol, Fatih Akcay, Ferah Armutcu, Liang-Yin Ke, Chu-Huang Chen
Cardiovascular disease (CVD) is a health problem of great concern to both the public and medical authorities. Low-density lipoprotein (LDL) has been reported to play an important role in both the development and progression of CVD, but studies are underway to determine how LDL exerts its effects. In recent years, it has been found that LDL has several subfractions, each of which affects endothelial function differently; L5, the most electronegative fraction, has been shown to be unique in that it induces an atherogenic response...
May 2017: Trends in Cardiovascular Medicine
Chun-Wun Lu, Yi-Hsuan Lo, Chu-Huang Chen, Ching-Yi Lin, Chun-Hao Tsai, Po-Jung Chen, Yi-Fang Yang, Chie-Hong Wang, Chun-Hsiang Tan, Ming-Feng Hou, Shyng-Shiou F Yuan
Abnormal lipoprotein profiles are associated with breast cancer progression. However, the mechanisms linking abnormal lipoprotein levels to breast cancer progression, especially metastasis, remain unclear. Herein, we found that L1 and L5 subfractions of LDL and VLDL, but not HDL, enhanced breast cancer cell viability. L1, L5, and VLDL also increased the in vitro tumorigenesis of breast cancer cells in anchorage-independent soft agar assay. In addition, L1, L5, and VLDL, but not HDL, increased the levels of mesenchymal markers Slug, Vimentin, and β-Catenin, and promoted breast cancer cell migration and invasion...
March 1, 2017: Cancer Letters
Chih-Sheng Chu, Liang-Yin Ke, Hua-Chen Chan, Hsiu-Chua Chan, Chih-Chieh Chen, Kai-Hung Cheng, Hsiang-Chun Lee, Hsuan-Fu Kuo, Ching-Tang Chang, Kuan-Cheng Chang, Sheng-Hsiung Sheu, Chu-Huang Chen, Wen-Ter Lai
BACKGROUND: Significantly higher cytotoxic and thrombogenic human electronegative low-density lipoprotein (LDL), or L5, has been found in patients with stable coronary artery disease and acute coronary syndrome. We hypothesized that the statin-benefit groups (SBGs) defined by the new cholesterol guideline were of higher electronegative L5. METHODS: In total, 62 hyperlipidemia patients (mean age 59.4 ± 10.5, M/F 40/22) were retrospectively divided into SBGs (n = 44) and N-SBGs (n = 18)...
November 2016: Acta Cardiologica Sinica
Chao-Hung Chen, Liang-Yin Ke, Hua-Chen Chan, An-Sheng Lee, Kun-Der Lin, Chih-Sheng Chu, Mei-Yueh Lee, Pi-Jung Hsiao, Chin Hsu, Chu-Huang Chen, Shyi-Jang Shin
Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells...
August 2016: Journal of Lipid Research
Chiz-Tzung Chang, Guei-Jane Wang, Chin-Chi Kuo, Ju-Yi Hsieh, An-Sean Lee, Chia-Ming Chang, Chun-Cheng Wang, Ming-Yi Shen, Chiu-Ching Huang, Tatsuya Sawamura, Chao-Yuh Yang, Nicole Stancel, Chu-Huang Chen
Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients.The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1-L5, with increasing electronegativity...
January 2016: Medicine (Baltimore)
Ming-Yi Shen, Fang-Yu Chen, Jing-Fang Hsu, Ru-Huei Fu, Chia-Ming Chang, Chiz-Tzung Chang, Chung-Hsiang Liu, Jia-Rong Wu, An-Sheng Lee, Hua-Chen Chan, Joen-Rong Sheu, Shinn-Zong Lin, Woei-Cherng Shyu, Tatsuya Sawamura, Kuan-Cheng Chang, Chung Y Hsu, Chu-Huang Chen
L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke...
March 10, 2016: Blood
Kathrin Hueging, Romy Weller, Mandy Doepke, Gabrielle Vieyres, Daniel Todt, Benno Wölk, Florian W R Vondran, Robert Geffers, Chris Lauber, Lars Kaderali, François Penin, Thomas Pietschmann
Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins...
2015: PloS One
Wei-Yu Chen, Fang-Yu Chen, An-Sheng Lee, Kuan-Hsiang Ting, Chia-Ming Chang, Jing-Fang Hsu, Wei-Shine Lee, Joen-Rong Sheu, Chu-Huang Chen, Ming-Yi Shen
Highly electronegative low-density lipoprotein (LDL) L5 induces endothelial cell (EC) apoptosis, which leads to the development of atherosclerosis. We examined the effects of sesamol (1), a natural organic component of sesame oil, on plasma L5 levels and atherosclerosis development in a rodent model and on the L5-induced apoptosis of ECs. Syrian hamsters, which have an LDL profile similar to that of humans, were fed a normal chow diet (control), a high-fat diet (HFD), or a HFD supplemented with the administration of 50 or 100 mg/kg of 1 via oral gavage (HFD+1) for 16 weeks (n = 8 per group)...
February 27, 2015: Journal of Natural Products
Jing-Fang Hsu, Tzu-Chieh Chou, Jonathan Lu, Shu-Hua Chen, Fang-Yu Chen, Ching-Chu Chen, Jeffrey L Chen, MacArthur Elayda, Christie M Ballantyne, Steven Shayani, Chu-Huang Chen
BACKGROUND: Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD...
2014: PloS One
An-Sheng Lee, Wei-Yu Chen, Hua-Chen Chan, Jing-Fang Hsu, Ming-Yi Shen, Chia-Ming Chang, Henry Bair, Ming-Jai Su, Kuan-Cheng Chang, Chu-Huang Chen
BACKGROUND: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage. METHODS: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS...
2014: Cardiovascular Diabetology
Fars K Alanazi, Nazrul Haq, Awwad A Radwan, Ibrahim A Alsarra, Faiyaz Shakeel
It has been reported that cholesterol-rich nanoemulsions (LDE) can bind to low density lipoprotein (LDL) receptors which can concentrate anticancer drugs in the tissues via LDL receptor overexpression and reduced the adverse effects of the treatment. Therefore, in this study, LDE nanoemulsions of cholesteryl-maleoyl-5-fluorouracil (5-FU conjugate) were developed and evaluated in vitro. LDE nanoemulsions were prepared by high-energy emulsification technique. Developed formulations were characterized in terms of droplet size, polydispersity index, zeta potential, viscosity and refractive index...
May 2015: Pharmaceutical Development and Technology
Timothy C Nichols
In this issue of Blood, Chan et al have described mechanisms by which L5, the most electronegative of 5 recognized fractions of low density lipoprotein (LDL), activates both platelets and endothelium in a manner that supports thrombosis and could possibly produce ST-elevation myocardial infarctions (STEMI).
November 21, 2013: Blood
Liang-Yin Ke, David A Engler, Jonathan Lu, Risë K Matsunami, Hua-Chen Chan, Guei-Jane Wang, Chao-Yuh Yang, Jan-Gowth Chang, Chu-Huang Chen
Anion-exchange chromatography resolves human plasma low-density lipoprotein (LDL) into 5 subfractions, with increasing negative surface charge in the direction of L1 to L5. Unlike the harmless L1 to L4, the exclusively atherogenic L5 is rejected by the normal LDL receptor (LDLR) but endocytosed into vascular endothelial cells through the lectin-like oxidized LDL receptor-1 (LOX-1). Analysis with SDS-PAGE and 2-dimensional electrophoresis showed that the protein framework of L1 was composed mainly of apolipoprotein (apo) B100, with an isoelectric point (pI) of 6...
2011: Pure and Applied Chemistry. Chimie Pure et Appliquée
Hua-Chen Chan, Liang-Yin Ke, Chih-Sheng Chu, An-Sheng Lee, Ming-Yi Shen, Miguel A Cruz, Jing-Fang Hsu, Kai-Hung Cheng, Hsiu-Chuan Bonnie Chan, Jonathan Lu, Wen-Ter Lai, Tatsuya Sawamura, Sheng-Hsiung Sheu, Jeng-Hsien Yen, Chu-Huang Chen
Platelet activation and aggregation underlie acute thrombosis that leads to ST-elevation myocardial infarction (STEMI). L5-highly electronegative low-density lipoprotein (LDL)-is significantly elevated in patients with STEMI. Thus, we examined the role of L5 in thrombogenesis. Plasma LDL from patients with STEMI (n = 30) was chromatographically resolved into 5 subfractions (L1-L5) with increasing electronegativity. In vitro, L5 enhanced adenosine diphosphate-stimulated platelet aggregation twofold more than did L1 and induced platelet-endothelial cell (EC) adhesion...
November 21, 2013: Blood
Chih-Sheng Chu, Yu-Chen Wang, Long-Sheng Lu, Brian Walton, H Ramazan Yilmaz, Roger Y Huang, Tatsuya Sawamura, Richard A F Dixon, Wen-Ter Lai, Chu-Huang Chen, Jonathan Lu
OBJECTIVES: Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. METHODS AND RESULTS: Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL cholesterol [LDL-C] levels, 154...
2013: PloS One
Po-Yuan Chang, Yi-Jie Chen, Fu-Hsiung Chang, Jonathan Lu, Wen-Huei Huang, Tzu-Ching Yang, Yuan-Teh Lee, Shwu-Fen Chang, Shao-Chun Lu, Chu-Huang Chen
AIMS: L5 is the most negatively charged subfraction of human low-density lipoprotein (LDL) and is the only subfraction of LDL capable of inducing apoptosis in cultured vascular endothelial cells (ECs) by inhibiting fibroblast growth factor-2 (FGF2) transcription. We examined whether plasma L5 levels are elevated in patients with ST-segment elevation myocardial infarction (STEMI) and whether aspirin provides epigenetic protection of human coronary artery ECs (HCAECs) exposed to L5. METHODS AND RESULTS: Plasma L5 levels were compared between patients with STEMI (n = 10) and control subjects with chest pain syndrome but a normal coronary arteriogram (n = 5)...
July 1, 2013: Cardiovascular Research
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