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- Benson, Tyler W, et al.
(författare)
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Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
- 2023
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Ingår i: bioRxiv : the preprint server for biology.
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.
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- Barbaro, M, et al.
(författare)
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Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia
- 2012
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 77:2, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aim:</i>X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the <i>NR0B1 </i>gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize <i>NR0B1</i> deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes. <i>Results:</i>In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the <i>GK</i> gene. A deletion extending to <i>IL1RAPL1</i> was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed. <i>Conclusions:</i>Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect <i>NR0B1</i> and contiguous gene deletions in patients with AHC. It is especially helpful for <i>IL1RAPL1 </i>deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy.
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- Jakobsson, Martin, et al.
(författare)
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Ryder Glacier in northwest Greenland is shielded from warm Atlantic water by a bathymetric sill
- 2020
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- The processes controlling advance and retreat of outlet glaciers in fjords draining the Greenland Ice Sheet remain poorly known, undermining assessments of their dynamics and associated sea-level rise in a warming climate. Mass loss of the Greenland Ice Sheet has increased six-fold over the last four decades, with discharge and melt from outlet glaciers comprising key components of this loss. Here we acquired oceanographic data and multibeam bathymetry in the previously uncharted Sherard Osborn Fjord in northwest Greenland where Ryder Glacier drains into the Arctic Ocean. Our data show that warmer subsurface water of Atlantic origin enters the fjord, but Ryder Glacier’s floating tongue at its present location is partly protected from the inflow by a bathymetric sill located in the innermost fjord. This reduces under-ice melting of the glacier, providing insight into Ryder Glacier’s dynamics and its vulnerability to inflow of Atlantic warmer water.
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