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Sökning: WFRF:(Courtney M. J.) > Glycoprotein VI is ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003987naa a2200577 4500
001oai:DiVA.org:uu-514557
003SwePub
008231018s2023 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5145572 URI
0247 a https://doi.org/10.1101/2023.07.02.5473612 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Benson, Tyler W4 aut
2451 0a Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
264 1c 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.
7001 a Pike, Mindy M4 aut
7001 a Spuzzillo, Anthony4 aut
7001 a Hicks, Sarah M4 aut
7001 a Pham, Michael4 aut
7001 a Mix, Doran S4 aut
7001 a Brunner, Seth I4 aut
7001 a Wadding-Lee, Caris4 aut
7001 a Conrad, Kelsey A4 aut
7001 a Russell, Hannah M4 aut
7001 a Jennings, Courtney4 aut
7001 a Coughlin, Taylor M4 aut
7001 a Aggarwal, Anu4 aut
7001 a Lyden, Sean4 aut
7001 a Mani, Kevinu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)kevma940
7001 a Björck, Martinu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)mabjo425
7001 a Wanhainen, Andersu Uppsala universitet,Kärlkirurgi4 aut0 (Swepub:uu)anwan103
7001 a Bhandari, Rohan4 aut
7001 a Lipworth-Elliot, Loren4 aut
7001 a Robinson-Cohen, Cassianne4 aut
7001 a Caputo, Francis J4 aut
7001 a Shim, Sharon4 aut
7001 a Edwards, Todd L4 aut
7001 a Tranter, Michael4 aut
7001 a Gardiner, Elizabeth E4 aut
7001 a Mackman, Nigel4 aut
7001 a Cameron, Scott J4 aut
7001 a Owens, A Phillip4 aut
7102 a Uppsala universitetb Kärlkirurgi4 org
7730 t bioRxiv : the preprint server for biology
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-514557
8564 8u https://doi.org/10.1101/2023.07.02.547361

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