4.7 Article

Binding of Oxidized Low-Density Lipoprotein on Circulating Platelets Is increased in Patients With Acute Coronary Syndromes and Induces Platelet Adhesion to Vascular Wall In Vivo-Brief Report

Journal

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 32, Issue 8, Pages 2017-U626

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.111.244707

Keywords

oxidized low-density lipoprotein; platelets; adhesion; acute coronary syndromes; thrombosis

Funding

  1. University of Tubingen
  2. Deutsche Forschungsgemeinschaft [TR-SFB19]
  3. Klinische Forschergruppe KFO [274]
  4. Volkswagen Foundation
  5. Wilhelm-Sander foundation

Ask authors/readers for more resources

Objective-Hyperlipidemia is associated with platelet hyperactivity. In the present study, we evaluated the binding of oxidized low-density lipoprotein (oxLDL) on the surface of circulating platelets in patients with stable coronary artery disease and acute coronary syndromes and its possible association with platelet activation. Furthermore, the role of oxLDL binding on platelet adhesion to collagen and endothelial cells in vitro as well as after carotid ligation in mice was investigated. Methods and Results-Using flow cytometry, patients with acute coronary syndromes (n= 174) showed significantly enhanced oxLDL binding compared with patients with stable coronary artery disease (n= 182; P= 0.007). Platelet-bound oxLDL positively correlated with the degree of platelet activation (expression of P-selectin and activated fibrinogen receptor; P<0.001 for both). Plasma oxLDL was increased in patients with acute coronary syndromes compared with stable angina pectoris patients. Preincubation of isolated platelets with oxLDL, but not with native LDL, resulted in enhanced platelet adhesion to collagen and activated endothelial cells under high shear stress in vitro, as well as after carotid ligation in C57BL/6J mice and apolipoprotein E-/- mice fed a high cholesterol diet. Conclusion-Increased platelet-bound oxLDL in patients with acute coronary syndromes may play an important role in atherothrombosis, thus providing a potential future therapeutic target. (Arterioscler Thromb Vasc Biol. 2012;32:2017-2020.)

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Rheumatology

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome

Maria G. Tektonidou, Evrydiki Kravvariti, Nikolaos Vlachogiannis, Georgios Georgiopoulos, Aimilia Mantzou, Petros P. Sfikakis, Konstantinos Stellos, Kimon Stamatelopoulos

Summary: In patients with Antiphospholipid Syndrome (APS), elevated plasma levels of Aβ40 are associated with adverse thrombo-inflammatory profile, and independently correlated with recurrent arterial events. Aβ40 levels provide additional value in improving the discrimination ability for recurrent arterial thromboses over the validated risk score aGAPSS in APS.

RHEUMATOLOGY (2021)

Editorial Material Cardiac & Cardiovascular Systems

Scientists on the Spot: RNA modifications in atherosclerosis

Monika Gladka, Konstantinos Stellos

CARDIOVASCULAR RESEARCH (2021)

Article Hematology

Circulating Amyloid Beta 1-40 Is Associated with Increased Rate of Progression of Atherosclerosis in Menopause: A Prospective Cohort Study

Irene Lambrinoudaki, Dimitrios Delialis, Georgios Georgiopoulos, Simon Tual-Chalot, Nikolaos I. Vlachogiannis, Raphael Patras, Evmorfia Aivalioti, Eleni Armeni, Areti Augoulea, Nikolaos Tsoltos, Anastasia Soureti, Konstantinos Stellos, Kimon Stamatelopoulos

Summary: Elevated levels of Alpha beta 1-40 may be associated with the progression of atherosclerosis in postmenopausal women. Patterns of persistently high or increasing Alpha beta 1-40 levels could be linked to accelerated subclinical atherosclerosis progression.

THROMBOSIS AND HAEMOSTASIS (2021)

Review Pharmacology & Pharmacy

Complement, inflammation and thrombosis

Elias Rawish, Manuela Sauter, Reinhard Sauter, Henry Nording, Harald F. Langer

Summary: This review explores the mutual relationship between immune activation and thrombus formation mechanisms, particularly focusing on how the complement system can modulate platelet activation. While some components of the complement system have been associated with platelets and shown to be functionally active in the micromilieu of platelet activation, the exact regulatory mechanisms and the consequences on tissue inflammation, damage, or recovery are still to be fully understood.

BRITISH JOURNAL OF PHARMACOLOGY (2021)

Article Multidisciplinary Sciences

The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets

Henry Nording, Lasse Baron, David Haberthuer, Frederic Emschermann, Matthias Mezger, Manuela Sauter, Reinhard Sauter, Johannes Patzelt, Kai Knoepp, Anne Nording, Moritz Meusel, Roza Meyer-Saraei, Ruslan Hlushchuk, Daniel Sedding, Oliver Borst, Ingo Eitel, Christian M. Karsten, Robert Feil, Bernd Pichler, Jeanette Erdmann, Admar Verschoor, Emmanouil Chavakis, Triantafyllos Chavakis, Philipp von Hundelshausen, Joerg Koehl, Meinrad Gawaz, Harald F. Langer

Summary: This study reveals that platelets negatively modulate revascularization through C5aR1 activation, inhibiting endothelial cell functions. By identifying the C5a/C5aR1-CXCL4 axis in platelets, a mechanism for controlling tissue neovascularization has been uncovered.

NATURE COMMUNICATIONS (2021)

Article Hematology

Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation

Malgorzata Cebo, Kristina Dittrich, Xiaoqing Fu, Mailin C. Manke, Frederic Emschermann, Johannes Rheinlaender, Hendrik von Eysmondt, Nerea Ferreiros, Jessica Sudman, Alexander Witte, Lisann Pelzl, Oliver Borst, Tobias Geisler, Dominik Rath, Tamam Bakchoul, Meinrad Gawaz, Tilman E. Schaeffer, Michael Laemmerhofer, Madhumita Chatterjee

Summary: Platelet ACKR3/CXCR7 surface expression is enhanced in coronary artery disease (CAD) patients, and it influences the prognosis. This study shows that ACKR3/CXCR7 regulates thromboinflammatory response by impacting the platelet lipidome. The findings suggest that ACKR3/CXCR7 may be a potential therapeutic target for cardiovascular diseases and CAD.

BLOOD (2022)

Article Biochemistry & Molecular Biology

Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation

Jeremy A. Nestele, Anne-Katrin Rohlfing, Valerie Dicenta, Alexander Bild, Daniela Eissler, Frederic Emschermann, Marcel Kremser, Konstantin Krutzke, Tilman E. Schaeffer, Oliver Borst, Moran Levi, Netanel Korin, Meinrad Paul Gawaz

Summary: Nanoparticles provide a novel approach for targeted antithrombotic therapy, delivering drugs to specific sites with low side effects. In this study, nanoparticles combined with established proteins successfully inhibited platelet aggregation and thrombus formation, indicating a promising therapeutic strategy for antithrombotic treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Multidisciplinary Sciences

Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis

Manuela Sauter, Reinhard J. Sauter, Henry Nording, Chaolan Lin, Marcus Olbrich, Stella Autenrieth, Christian Gleissner, Martin Thunemann, Nadia Otero, Esther Lutgens, Zouhair Aherrahrou, Dennis Wolf, Lars Zender, Sven Meuth, Robert Feil, Harald F. Langer

Summary: This study investigated the role of CD11c(+) cells in atherosclerosis. The results showed that CD11c(+) cells alleviate atherosclerosis by secreting ApoE, and the level of ApoE derived from CD11c(+) cells is associated with the burden of atherosclerotic plaques.

ISCIENCE (2022)

Article Immunology

Activated Platelets Upregulate b2 Integrin Mac-1 (CD11b/CD18) on Dendritic Cells, Which Mediates Heterotypic Cell-Cell Interaction

Henry Nording, Manuela Sauter, Chaolan Lin, Rebecca Steubing, Sven Geisler, Ying Sun, Joel Niethammer, Frederic Emschermann, Yunmei Wang, Barbara Zieger, Bernhard Nieswandt, Christoph Kleinschnitz, Daniel I. Simon, Harald F. Langer

Summary: Recent evidence supports the interaction between platelets and dendritic cells (DCs), but the molecular mechanisms underlying this heterotypic cell cross-talk remain largely unknown. In this study, the researchers found that activated platelets can enhance the binding between human monocyte-derived DCs and platelets in a dynamic incubation model. Inhibition of CD11b and GPIba significantly reduced the adhesion between DCs and platelets in vitro, and the same inhibition also decreased platelet-mediated DC adhesion to the injured arterial wall in vivo.

JOURNAL OF IMMUNOLOGY (2022)

Review Physiology

Targeting Cell-Specific Molecular Mechanisms of Innate Immunity in Atherosclerosis

M. Sauter, H. F. Langer

Summary: This article investigates the contribution of innate immune mechanisms to atherosclerosis and their interaction with molecules of cholesterol homeostasis. Recent research has identified potential roles of previously overlooked cell types, such as platelets and dendritic cells, in this chronic disease. However, specific therapeutic approaches targeting these immune mechanisms have not yet been successfully introduced into everyday clinical practice.

FRONTIERS IN PHYSIOLOGY (2022)

Article Hematology

Platelets regulate ischemia-induced revascularization and angiogenesis by secretion of growth factor-modulating factors

Henry Nording, Lasse Baron, Manuela Sauter, Antje Luebken, Elias Rawish, Rebecca Szepanowski, Jacob von Esebeck, Ying Sun, Hossein Emami, Moritz Meusel, Roza Saraei, Nancy Schanze, Sivahari Prasad Gorantla, Nikolas von Bubnoff, Tobias Geisler, Philipp von Hundelshausen, Konstantinos Stellos, Jens Marquardt, Christian D. Sadik, Joerg Koehl, Daniel Duerschmied, Christoph Kleinschnitz, Harald F. Langer

Summary: Platelets modulate angiogenesis in ischemic tissue through activation of C5a receptor 1 (C5aR1). The presence of C5aR1-expressing platelets is increased in ischemic hindlimb, and ischemia-driven angiogenesis is significantly improved in C5aR1-/- mice. The inhibition of angiogenesis by platelets is mediated by the release of antiangiogenic CXCL4 through a paracrine mechanism, which depends on the activation of C5a-C5aR1 axis.

BLOOD ADVANCES (2023)

Article Immunology

Platelet depletion does not alter long-term functional outcome after cerebral ischaemia in mice

Rebecca D. Steubing, Fabian Szepanowski, Christina David, Ayan Mohamud Yusuf, Stine Mencl, Anne-Kathrin Mausberg, Harald F. Langer, Manuela Sauter, Cornelius Deuschl, Michael Forsting, Anke C. Fender, Dirk M. Hermann, Ana I. Casas, Friederike Langhauser, Christoph Kleinschnitz

Summary: Platelets play a critical role in thrombus formation and inflammation during acute ischemic stroke, but their contribution to long-term tissue reorganization and functional recovery appears to be marginal.

BRAIN, BEHAVIOR, & IMMUNITY - HEALTH (2022)

Article Biochemical Research Methods

Protocol to isolate and analyze mouse bone marrow derived dendritic cells (BMDC)

Manuela Sauter, Reinhard J. Sauter, Henry Nording, Marcus Olbrich, Frederic Emschermann, Harald F. Langer

Summary: This article describes an in vitro approach to analyze the role of CD11c+ cells and CD11c+-derived ApoE in atherosclerosis. The method involves harvesting mouse bone marrow, culturing the cells, treating them with differentiation factors, and collecting the cells after removing undesirable populations. This protocol can be adapted for different diseases and used to analyze cell-specific molecules.

STAR PROTOCOLS (2022)

Article Biochemical Research Methods

Protocol to visualize CD11c+ cells in atherosclerosis using LacZ reporter mice

Manuela Sauter, Reinhard J. Sauter, Marcus Olbrich, Martin Thunemann, Susanne Feil, Robert Feil, Harald F. Langer

Summary: In this article, an in vivo approach to visualize CD11c+ cells in atherosclerosis is described. The authors use X-Gal staining to analyze plaque composition and cell-specific molecules as an alternative method. By breeding mice with LacZ knockin and CD11ccre recombinase onto an ApoE-/- background, the interested cell type in the plaques can be visualized by X-Gal staining. This approach allows for the examination of various immune cells in atherogenesis.

STAR PROTOCOLS (2022)

No Data Available