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"lipoprotein (a)" and "endothelial cell"

Johan G Schnitzler, Geesje M Dallinga-Thie, Jeffrey Kroon
Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop distinct inflammatory and pro-atherogenic potential, leading to impaired endothelial behavior and subsequent increased foam cell formation. LDL can also directly affect circulating monocyte composition, rendering them in a more favorable position to migrate and accumulate in the subendothelial space...
March 16, 2018: Current Medicinal Chemistry
Elena Bargagli, Elisabetta Rosi, Massimo Pistolesi, Federico Lavorini, Luca Voltolini, Paola Rottoli
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Recent studies demonstrated that its pathogenesis is related with enhanced oxidative stress (protein carbonylation and lipid peroxidation) and alterations in the circulating lipid profile. Alterations of lipid metabolism (including the reduction in high-density lipoprotein cholesterol levels and apolipoprotein A1 concentrations) induce plasma membrane, bronchial and lung capillary endothelial cell damage in sarcoidosis patients. Dyslipidemia is associated with increased oxidative stress, diminished overall antioxidative protection and increased risk for atherosclerosis...
2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Yawei Shi, Xuesi Wan, Nan Shao, Runyi Ye, Ning Zhang, Yunjian Zhang
The present study aimed to determine the protective and anti-angiopathy effects of ginsenoside (GSS) on Wistar rats with diabetes mellitus (DM). Diabetic angiopathy occurs during the early stage of diabetes, and in type 1 DM (T1DM) and type 2 DM (T2DM). In the present study, early DM, T1DM and T2DM were induced by treatment with a high‑sucrose‑high‑fat diet, alloxan monohydrate or streptozocin, respectively. The levels of blood glucose, insulin, lipid metabolism markers [total cholesterol (TC), triglyceride (TG), high‑density lipoprotein (HDL) and lipoprotein(a) (Lp‑a)], and endothelial cell function markers [endothelin, nitric oxide, vascular endothelial growth factor (VEGF) and interleukin‑6 (IL‑6)] were determined following treatment with GSS...
November 2016: Molecular Medicine Reports
Guo-Hua Li, Xiao-Long Lin, Hai Zhang, Shuang Li, Xing-Lan He, Kai Zhang, Juan Peng, Ya-Ling Tang, Jun-Fa Zeng, Yue Zhao, Xiao-Feng Ma, Jian-Jun Lei, Ren Wang, Dang-Heng Wei, Zhi-Sheng Jiang, Zuo Wang
Oxidised lipoprotein(a) [oxLp(a)] is considered as a more potent arteriosclerotic factor than native Lp(a). However, the molecular mechanisms underlying this potency remain unclear. Reactive oxygen species (ROS) possibly act as intracellular second messengers that participate in autophagy stimulation. In this study, the effect of oxLp(a) on endothelial cell autophagy was determined. The mechanism and effect of autophagy on endothelial cells were also investigated. Results showed that oxLp(a) could induce autophagy depending on the generation of cellular ROS...
November 2015: Atherosclerosis
Yoko Haraguchi, Ryuji Toh, Minoru Hasokawa, Hideto Nakajima, Tomoyuki Honjo, Kazunori Otsui, Kenta Mori, Maki Miyamoto-Sasaki, Masakazu Shinohara, Kunihiro Nishimura, Tatsuro Ishida, Ken-Ichi Hirata
OBJECTIVE: Granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for high-density lipoprotein (HDL). We evaluated their effects on coronary risk stratification and function of lipoproteins. METHODS AND RESULTS: A total 158 patients who had previously undergone percutaneous coronary intervention and who had been hospitalized for coronary re-angiography were enrolled. Coronary lesions (restenosis or de novo lesion) were observed in 84 patients but not associated with conventional lipid profile...
June 2014: Atherosclerosis
Rocco Romagnuolo, Santica M Marcovina, Michael B Boffa, Marlys L Koschinsky
Apo(a), the distinguishing protein component of lipoprotein(a) [Lp(a)], exhibits sequence similarity to plasminogen and can inhibit binding of plasminogen to cell surfaces. Plasmin generated on the surface of vascular cells plays a role in cell migration and proliferation, two of the fibroproliferative inflammatory events that underlie atherosclerosis. The ability of apo(a) to inhibit pericellular plasminogen activation on vascular cells was therefore evaluated. Two isoforms of apo(a), 12K and 17K, were found to significantly decrease tissue-type plasminogen activator-mediated plasminogen activation on human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes and macrophages...
April 2014: Journal of Lipid Research
Rachelle E Kaplon, Lindsey B Gano, Douglas R Seals
We tested the hypothesis that vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults. In 127 men and women aged 48-77 yr, brachial artery flow-mediated dilation (FMD) was positively related to dietary niacin intake [%change (Δ): r = 0.20, P < 0.05; mmΔ: r = 0.25, P < 0.01]. In subjects with above-average dietary niacin intake (≥ 22 mg/day, NHANES III), FMD was 25% greater than in subjects with below-average intake (P < 0...
January 15, 2014: Journal of Applied Physiology
Daniel A Mulrooney, Kirsten K Ness, Sujuan Huang, Anna Solovey, Robert P Hebbel, James D Neaton, Denis R Clohisy, Aaron S Kelly, Joseph P Neglia
BACKGROUND: Cardiovascular-related toxicities have been reported among survivors of osteosarcoma. METHODS: Fasting blood samples from 24 osteosarcoma survivors were analyzed for high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein-ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and surface expression of vascular cell adhesion molecule-1 (VCAM-1). Values were compared to subjects in the natural history Coronary Artery Risk Development in Young Adults (CARDIA) cohort study except for CECs and VCAM-1 expression, which were compared to controls studied at the University of Minnesota Lillehei clinical trials unit...
October 2013: Pediatric Blood & Cancer
Deng-heng Wei, Xiao-lei Zhang, Ren Wang, Jun-fa Zeng, Kai Zhang, Jian Yang, Shuang Li, Xiao-long Lin, Zhi-sheng Jiang, Gui-xue Wang, Zuo Wang
Oxidized lipoprotein(a) (oxLp(a)) is a more potent marker of atherogenesis than native Lp(a). However, the molecular mechanisms of oxLp(a) activity are not clear. Reactive oxygen species (ROS) have recently been suggested as acting as intracellular second messengers. In this study, the effects of oxLp(a) on endothelial cell monolayer permeability and the role of reactive oxygen species (ROS) generation in these effects were investigated. Our results showed that oxLp(a) inhibited desmoglein-1 (DSG1) and desmocollin-2 (DSC2) expression at both mRNA and protein levels in a dose- and time-dependent manner, and increased the generation of cellular ROS...
June 2013: Lipids
Maria do Sameiro Faria, Sandra Ribeiro, Petronila Rocha-Pereira, Vasco Miranda, Alexandre Quintanilha, Flávio Reis, Elísio Costa, Luís Belo, Alice Santos-Silva
PURPOSE: The aim of this work was to assess the effect of statin therapy on inflammatory and fibrinolytic/endothelial (dys)function markers in end-stage renal disease (ESRD) patients under hemodialysis (HD), according to the type of vascular access. METHODS: This transversal study includes 191 ESRD patients under regular HD, divided into four groups according to vascular access and statin therapy: 87 patients with arteriovenous fistula (AVF) and no statins (AVF-NS), 61 with AVF and statins (AVF-S), 27 with central venous dialysis catheter (CVC) and no statins (CVC-NS) and 16 with CVC and statins (CVC-S)...
October 2013: Journal of Vascular Access
Michele Malaguarnera, Marco Vacante, Cristina Russo, Giulia Malaguarnera, Tijana Antic, Lucia Malaguarnera, Rita Bella, Giovanni Pennisi, Fabio Galvano, Alessandro Frigiola
Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator...
2013: BioMed Research International
Henning Morawietz, Winfried Goettsch, Melanie Brux, Manja Reimann, Stefan R Bornstein, Ulrich Julius, Tjalf Ziemssen
OBJECTIVE: Hypercholesterolemia is an important risk factor of cardiovascular diseases. Lipoprotein apheresis is an efficient strategy to reduce the serum low-density lipoprotein (LDL)-cholesterol and lipoprotein(a) levels and cardiovascular complications in patients with severe hypercholesterolemia. The underlying molecular mechanisms are not well-understood. In this study, we analyzed the impact of lipoprotein apheresis on gene expression in human endothelial cells. METHODS: Human endothelial cells were stimulated with serum of hypercholesterolemic patients before and after lipoprotein apheresis...
January 2013: Atherosclerosis. Supplements
Lei Liu, Michael B Boffa, Marlys L Koschinsky
Elevated plasma concentrations of lipoprotein(a) are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a), the unique glycoprotein component of lipoprotein(a), is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin...
2013: PloS One
Taewoo Cho, Rocco Romagnuolo, Corey Scipione, Michael B Boffa, Marlys L Koschinsky
Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease risk. This may be attributable to the ability of Lp(a) to elicit endothelial dysfunction. We previously reported that apolipoprotein(a) (apo(a); the distinguishing kringle-containing component of Lp(a)) elicits cytoskeletal rearrangements in vascular endothelial cells, resulting in increased cellular permeability. These effects require a strong lysine-binding site (LBS) in apo(a). We now report that apo(a) induces both nuclear β-catenin-mediated cyclooxygenase-2 (COX-2) expression and prostaglandin E2 secretion, indicating a proinflammatory role for Lp(a)...
February 2013: Molecular Biology of the Cell
Ashley E Walker, Rachelle E Kaplon, Sara Marian S Lucking, Molly J Russell-Nowlan, Robert H Eckel, Douglas R Seals
Vascular endothelial dysfunction develops with aging, as indicated by impaired endothelium-dependent dilation, and is related to increased cardiovascular disease risk. We hypothesized that short-term treatment with fenofibrate, a lipid-lowering agent with potential pleiotropic effects, would improve endothelium-dependent dilation in middle-aged and older normolipidemic adults by reducing oxidative stress. Brachial artery flow-mediated dilation, a measure of endothelium-dependent dilation, was assessed in 22 healthy adults aged 50 to 77 years before and after 7 days of fenofibrate (145 mg/d; n=12) or placebo (n=10)...
December 2012: Hypertension
Kirsten Riches, Karen E Porter
Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of cardiovascular disease (CVD). Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a) apart from plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a) (apo(a)), both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC) and endothelial cells (EC))...
2012: Cholesterol
José L Sánchez-Quesada, Sandra Villegas, Jordi Ordóñez-Llanos
PURPOSE OF REVIEW: Subendothelial retention of lipoproteins is considered the first step in the development of atherosclerosis, but the molecular mechanisms involved are poorly understood. Recent findings on the atherogenic properties of a minor electronegative fraction of LDL (LDL(-)) could contribute to a better understanding of this process. RECENT FINDINGS: Circular dichroism, Trp-fluorescence and two-dimensional nuclear magnetic resonance have shown that apolipoprotein B (apoB) in LDL(-) has an abnormal, misfolded conformation...
October 2012: Current Opinion in Lipidology
Dimitrios Kirmizis, Aikaterini Papagianni, Fani Dogrammatzi, Anna-Maria Belechri, Efstathios Alexopoulos, Georgios Efstratiadis, Dimitrios Memmos
BACKGROUND: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes. METHODS: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period...
2012: Renal Failure
Masaaki Iwabayashi, Yoshiaki Taniyama, Fumihiro Sanada, Junya Azuma, Kazuma Iekushi, Keita Okayama, Amarnath Chatterjee, Hiromi Rakugi, Ryuichi Morishita
BACKGROUND: Lipoprotein (a) (Lp(a)) is one of the risk factors for peripheral artery disease (PAD). Our previous report demonstrated that hepatocyte growth factor (HGF) gene therapy attenuated the impairment of collateral formation in Lp(a) transgenic mice. Since risk factors for atherosclerosis accelerate endothelial senescence and impair angiogenesis, we examined the role of Lp(a) in dysfunction and senescence of endothelial progenitor cells (EPC) and endothelial cells. METHODS: In vitro and in vivo incorporation assays were performed using ex-vivo expanded DiI-labeled human EPC...
June 22, 2012: Biochemical and Biophysical Research Communications
Daniel A Mulrooney, Kirsten K Ness, Anna Solovey, Robert P Hebbel, James D Neaton, Bruce A Peterson, Chung K K Lee, Aaron S Kelly, Joseph P Neglia
BACKGROUND: Vascular-related toxicities have been reported among survivors of Hodgkin lymphoma (HL), but their genesis is not well understood. PROCEDURE: Fasting blood samples from 25 previously irradiated HL survivors were analyzed for biomarkers that can reveal underlying inflammation and/or endothelial cell activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion molecule-1 (VCAM-1) expression...
August 2012: Pediatric Blood & Cancer
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