Publications by authors named "I Krueger"

Introduction: Platelet activation and thrombus formation is crucial for hemostasis, but also trigger arterial thrombosis. Calcium mobilization plays an important role in platelet activation, because many cellular processes depend on the level of intracellular Ca ([Ca](i)), such as integrin activation, degranulation, cytoskeletal reorganization. Different modulators of Ca signaling have been implied, such as STIM1, Orai1, CyPA, SGK1, etc.

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Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms.

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Article Synopsis
  • Vascular injury exposes the extracellular matrix (ECM) proteins, which are essential for platelet adhesion to prevent excessive bleeding, and biglycan is a key ECM protein regulating platelet activity.* -
  • Research using biglycan knockout mice and recombinant proteins showed that biglycan facilitates platelet adhesion and thrombus formation, activating the collagen receptor GPVI and reorganizing the platelet cytoskeleton.* -
  • The absence of biglycan in the vessel wall led to decreased platelet adhesion and longer bleeding times in mice, highlighting its critical role in hemostasis following vascular injury.*
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Cardiovascular diseases (CVDs) are the leading cause of death globally-partly a consequence of increased population size and ageing-and are major contributors to reduced quality of life. Platelets play a major role in hemostasis and thrombosis. While platelet activation and aggregation are essential for hemostasis at sites of vascular injury, uncontrolled platelet activation leads to pathological thrombus formation and provokes thrombosis leading to myocardial infarction or stroke.

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Objective: Reelin, a secreted glycoprotein, was originally identified in the central nervous system, where it plays an important role in brain development and maintenance. In the cardiovascular system, reelin plays a role in atherosclerosis by enhancing vascular inflammation and in arterial thrombosis by promoting platelet adhesion, activation, and thrombus formation via APP (amyloid precursor protein) and GP (glycoprotein) Ib. However, the role of reelin in hemostasis and arterial thrombosis is not fully understood to date.

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