Identification and characterization of LRP8 (apoER2) in human blood platelets

Riddell, David; Vinogradov, Dimitri V.; Stannard, Anita K.; Chadwick, Nicholas; Owen, James S.

doi:10.1016/s0022-2275(20)34910-5

Cited by 97 publications

(15 citation statements)

References 21 publications

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“…It improves the anti-coagulant balance by contributing to neutralize the side-effects of prothrombin on the barrier properties of the endothelial cells ( Sinha et al, 2016 ). Likewise, the activation of LRP8 in the platelets contributes to inhibit their aggregation ( Riddell et al, 1999 ). Moreover, LRP8 prevents VSMCs from acquiring a senescent, secretory, fibrotic phenotype ( Komaravolu et al, 2019 ).…”

Section: Brain Insulin-resistancementioning

confidence: 99%

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment

2021

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Compromise of the vascular system has important consequences on cognitive abilities and neurodegeneration. The identification of the main molecular signatures present in the blood vessels of human hippocampus could provide the basis to understand and tackle these pathologies. As direct vascular experimentation in hippocampus is problematic, we achieved this information by computationally disaggregating publicly available whole microarrays data of human hippocampal homogenates. Three conditions were analyzed: ‘Young Adults’, ‘Aged’, and ‘aged with Mild Cognitive Impairment’ (MCI). The genes identified were contrasted against two independent data-sets. Here we show that the endothelial cells from the Younger Group appeared in an ‘activated stage’. In turn, in the Aged Group, the endothelial cells showed a significant loss of response to shear stress, changes in cell adhesion molecules, increased inflammation, brain-insulin resistance, lipidic alterations, and changes in the extracellular matrix. Some specific changes in the MCI group were also detected. Noticeably, in this study the features arisen from the Aged Group (high tortuosity, increased bifurcations, and smooth muscle proliferation), pose the need for further experimental verification to discern between the occurrence of arteriogenesis and/or vascular remodeling by capillary arterialization. This article has an associated First Person interview with the first author of the paper.

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Section: Brain Insulin-resistancementioning

confidence: 99%

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment

2021

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“…A truncated splice variant of LRP-8, (LDL receptor related protein) (also known as ApoER2) is the only member of the LDL-receptor family present in platelets; thus, our interest was focused on this receptor protein. 16 We have recently shown that β 2 GPI-antibody complexes bind to LRP-8 and that binding activates platelets and induces thomboxane A2 synthesis. 17 Our in vitro experiments were confirmed in a mouse model of APS in which we found that a soluble fragment of the LRP-8 receptor was able to completely inhibit thrombus formation.…”

Section: Antiphospholipid Antibodies and Cell Activationmentioning

confidence: 99%

Pathogenic role of antiphospholipid antibodies

Salmon

Groot

2008

Lupus

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The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that APL antibodies alter regulation of haemostasis and induce activation of complement. We will discuss the current knowledge on how aPL antibodies trigger increased inflammation and enhanced thrombotic tendency, and thereby lead to tissue damage.

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“…37 The LDL-receptor family consists of nine family members. As a truncated splice variant of LRP-8 (also known as ApoER2), is the only member of the LDL-receptor family present on platelets, 38 our interest was focused on this receptor protein. We have now shown that β 2 GPI-antibody complexes can bind to LRP-8 and that this binding mediates the activation of platelets and the induction of thomboxane A2 synthesis.…”

Section: Antiphospholipid Antibodies and Plateletsmentioning

confidence: 99%

“…37,39 Interestingly, in the first publication on the role of LRP-8 in platelets, it was proposed that this receptor might be involved in inhibition of platelet function by Apolipoprotein E, one of its ligands. 38 In the two publications that followed shortly, LRP-8 was suggested to mediate the enhanced platelet aggregability observed after stimulation with two other ligands, LDL and the β 2 GPIantibody complex. 37,40 An explanation of these different observations could be the existence of different polymorphisms and of different splice variants known for LRP-8.…”

Section: Antiphospholipid Antibodies and Plateletsmentioning

confidence: 99%

Platelets and the antiphospholipid syndrome

Urbanus

Derksen

Groot

2008

Lupus

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The antiphospholipid syndrome is a non-inflammatory autoimmune disease characterised by the presence of antiphospholipid antibodies in the plasma of patients with venous or arterial thrombosis or recurrent complications of pregnancy. The strong relation between the presence of antibodies against anionic phospholipids and thrombo-embolic complications is well established, but how the presence of antiphospholipid antibodies results in the observed clinical manifestations remains a mystery. Experimental observations suggest that an altered regulation of platelet function can cause the thrombotic complications observed in the antiphospholipid syndrome. In this review, we will discuss the evidence that the platelet is an important player in the pathogenesis of the antiphospholipid syndrome.

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Identification and characterization of LRP8 (apoER2) in human blood platelets

Cited by 97 publications

References 21 publications

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment

Pathogenic role of antiphospholipid antibodies

Platelets and the antiphospholipid syndrome

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