Journal: Atherosclerosis

Abbreviation

Atherosclerosis (Amst.)

Publisher

Elsevier

Journal Volumes

ISSN

0021-9150

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Publications 1 - 10 of 21
  • Choosing the optimal wall shear parameter for the prediction of plaque location
    Item type: Journal Article
    Rikhtegar, Farhad; Knight, Joseph A.; Olgac, Ufuk; et al. (2012)
    Atherosclerosis
  • Development and validation of a novel 10-year residual risk score (RRS) in the UK Biobank and Massachusetts general Brigham populations for patients with established ASCVD
    Item type: Other Conference Item
    Mineeva, Olga; Li, Chunying; Giulianini, Franco; et al. (2024)
    Atherosclerosis
  • Mapping the dynamic high-density lipoprotein synapse
    Item type: Journal Article
    Frey, Kathrin; Rohrer, Lucia; Frommelt, Fabian; et al. (2023)
    Atherosclerosis
    Background and aims: Heterogeneous high-density lipoprotein (HDL) particles, which can contain hundreds of proteins, affect human health and disease through dynamic molecular interactions with cell surface proteins. How HDL mediates its long-range signaling functions and interactions with various cell types is largely unknown. Due to the complexity of HDL, we hypothesize that multiple receptors engage with HDL particles resulting in condition-dependent receptor-HDL interaction clusters at the cell surface. Methods: Here we used the mass spectrometry-based and light-controlled proximity labeling strategy LUX-MS in a discovery-driven manner to decode HDL-receptor interactions. Results: Surfaceome nanoscale organization analysis of hepatocytes and endothelial cells using LUX-MS revealed that the previously known HDL-binding protein scavenger receptor B1 (SCRB1) is embedded in a cell surface protein community, which we term HDL synapse. Modulating the endothelial HDL synapse, composed of 60 proteins, by silencing individual members, showed that the HDL synapse can be assembled in the absence of SCRB1 and that the members are interlinked. The aminopeptidase N (AMPN) (also known as CD13) was identified as an HDL synapse member that directly influences HDL uptake into the primary human aortic endothelial cells (HAECs). Conclusions: Our data indicate that preformed cell surface residing protein complexes modulate HDL function and suggest new theragnostic opportunities.
  • Comparative in vivo analysis of the atherosclerotic plaque targeting properties of eight human monoclonal antibodies
    Item type: Journal Article
    Fiechter, Michael; Frey, Katharina; Fugmann, Tim; et al. (2011)
    Atherosclerosis
  • Choosing the optimal wall shear parameter for the prediction of plaque location-A patient-specific computational study in human right coronary arteries
    Item type: Journal Article
    Knight, Joseph; Olgac, Ufuk; Saur, Stefan C.; et al. (2010)
    Atherosclerosis
  • Long-term dietary supplementation with plant-derived omega-3 fatty acid improves outcome in experimental ischemic stroke
    Item type: Journal Article
    Bonetti, Nicole R.; Liberale, Luca; Akhmedov, Alexander; et al. (2021)
    Atherosclerosis
    Background and aims Early revascularization -the gold standard therapy for ischemic stroke- is often withheld in the elderly population due to high risk of complications. Thus, safe and effective preventive and therapeutic options are needed. The plant-derived omega-3-fatty-acid alpha-linolenic-acid (ALA) has emerged as a novel cardiovascular-protective agent. As of yet, little is known about its potential therapeutic effects on stroke. We hereby aimed to investigate the impact of a clinically relevant long-term dietary intervention with ALA on stroke outcome. Methods Six month-old C57BL/6 wildtype males were either fed an ALA-rich (high ALA) or a control diet (low ALA) for 12 months. At 18 months, brain ischemia/reperfusion was induced by transient middle cerebral artery occlusion (tMCAO). Stroke size and neurological function were assessed. Functional blood-brain-barrier-(BBB) permeability and protein expression were assessed by immunohistochemistry. Baseline inflammatory markers were measured at 18 months. Results High ALA-fed animals displayed decreased circulating TNF-α levels and Neutrophil-to-Lymphocyte Ratios at 18 months. Stroke size and neurological dysfunction were significantly reduced in high ALA-fed animals. Coherently to the reduced stroke size, functional BBB integrity and occludin endothelial expression were maintained by high ALA supplementation. Additionally, ALA reduced endothelial activation and thus recruitment and activation of macrophages and resident microglia. Finally, high ALA diet reduced the expression of BBB-degrading and neurotoxic MMP-3 and MMP-9. Conclusions We demonstrate the beneficial effects of a clinically relevant and feasible dietary intervention with a safe and readily available compound in the setting of stroke. The protective effects observed with ALA supplementation may relate to blunting of inflammation and might pave the way for novel stroke treatments.
  • Targeting the Immune Co-Stimulatory Molecule CD80 for the Imaging of Vulnerable Atherosclerotic Plaques by Pet
    Item type: Other Conference Item
    Meletta, R.; Müller, A.; Mu, Linjing; et al. (2014)
    Atherosclerosis
  • Apolipoprotein M Modulates Erythrocyte Efflux And Urinary Excretion Of Sphingosine-1-Phosphate
    Item type: Other Conference Item
    Sutter, I.; Park, R.; Othman, A.; et al. (2014)
    Atherosclerosis
  • Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism
    Item type: Journal Article
    Karuna, Ratna; Holleboom, Adriaan G.; Motazacker, Mohammad M.; et al. (2011)
    Atherosclerosis
  • The U2-spliceosome and its interactors regulate the levels and activity of the LDL receptor in humans
    Item type: Other Journal Item
    Zanoni, Paolo; Othman, Alaa; Meier, Roger; et al. (2020)
    Atherosclerosis
    Background and Aims: The low-density lipoprotein receptor (LDLR) in the liver is the major determinant of LDL-cholesterol levels in humans. The discovery of novel genes that regulate the activity of LDLR could lead to the identification of pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. Methods: We performed a genome-wide RNAi screen for fluorescent LDL uptake in Huh-7 hepatocarcinoma cells and validated our top hit genes in vitro, ex vivo as well as in population genetics datasets. Results: In our genome-wide RNAi screen, the knock-down of 54 genes led to a significant inhibition of LDL uptake. Fifteen of these genes encode for proteins involved in splicing, especially components or interactors of the U2-spliceosome. Knocking down 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR. The transcript is translated into an LDLR fragment, which lacks 88% of the full length LDLR and is detectable in cells and their medium upon overexpression, but neither in non-transfected cells nor in human plasma. The intron 3 retention transcript is expressed in considerable amounts in human liver and in blood cells. Its expression correlates with plasma LDL-cholesterol and age and increases after bariatric surgery. Single nucleotide polymorphisms and rare variants of one spliceosome gene, RBM25, are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Conclusions: We identified a novel mechanism of post-transcriptional regulation of LDLR activity in humans.
Publications 1 - 10 of 21