Sökning: onr:"swepub:oai:DiVA.org:uu-514557" > Glycoprotein VI is ...
Fältnamn | Indikatorer | Metadata |
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000 | 03987naa a2200577 4500 | |
001 | oai:DiVA.org:uu-514557 | |
003 | SwePub | |
008 | 231018s2023 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5145572 URI |
024 | 7 | a https://doi.org/10.1101/2023.07.02.5473612 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Benson, Tyler W4 aut |
245 | 1 0 | a Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms. |
264 | 1 | c 2023 |
338 | a print2 rdacarrier | |
520 | a 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. | |
700 | 1 | a Pike, Mindy M4 aut |
700 | 1 | a Spuzzillo, Anthony4 aut |
700 | 1 | a Hicks, Sarah M4 aut |
700 | 1 | a Pham, Michael4 aut |
700 | 1 | a Mix, Doran S4 aut |
700 | 1 | a Brunner, Seth I4 aut |
700 | 1 | a Wadding-Lee, Caris4 aut |
700 | 1 | a Conrad, Kelsey A4 aut |
700 | 1 | a Russell, Hannah M4 aut |
700 | 1 | a Jennings, Courtney4 aut |
700 | 1 | a Coughlin, Taylor M4 aut |
700 | 1 | a Aggarwal, Anu4 aut |
700 | 1 | a Lyden, Sean4 aut |
700 | 1 | a Mani, Kevinu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)kevma940 |
700 | 1 | a Björck, Martinu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)mabjo425 |
700 | 1 | a Wanhainen, Andersu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)anwan103 |
700 | 1 | a Bhandari, Rohan4 aut |
700 | 1 | a Lipworth-Elliot, Loren4 aut |
700 | 1 | a Robinson-Cohen, Cassianne4 aut |
700 | 1 | a Caputo, Francis J4 aut |
700 | 1 | a Shim, Sharon4 aut |
700 | 1 | a Edwards, Todd L4 aut |
700 | 1 | a Tranter, Michael4 aut |
700 | 1 | a Gardiner, Elizabeth E4 aut |
700 | 1 | a Mackman, Nigel4 aut |
700 | 1 | a Cameron, Scott J4 aut |
700 | 1 | a Owens, A Phillip4 aut |
710 | 2 | a Uppsala universitetb Kärlkirurgi4 org |
773 | 0 | t bioRxiv : the preprint server for biology |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-514557 |
856 | 4 8 | u https://doi.org/10.1101/2023.07.02.547361 |
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