Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target
- PMID: 38900973
- PMCID: PMC11522893
- DOI: 10.1182/blood.2023021655
Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target
Abstract
A common feature in patients with abdominal aortic aneurysms (AAAs) 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 affects the pathogenesis of AAA. Using RNA sequencing, we identified that the platelet-associated transcripts are significantly enriched in the ILT compared with 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 patients with AAAs. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in 2 independent cohorts of patients with AAAs is highly predictive of an AAA diagnosis and associates more strongly with aneurysm growth rate than D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in 2 independent mouse models. In conclusion, we show that the 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, for which none currently exists.
© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Conflict of interest statement
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Comment in
-
Platelets burst your bubble.Blood. 2024 Oct 17;144(16):1649-1650. doi: 10.1182/blood.2024025270. Blood. 2024. PMID: 39418034 No abstract available.
References
-
- Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2004;24:429–434. - PubMed
-
- Summers KL, Kerut EK, Sheahan CM, Sheahan MG., 3rd Evaluating the prevalence of abdominal aortic aneurysms in the United States through a national screening database. J Vasc Surg. 2021;73(1):61–68. - PubMed
-
- Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67:2–77.e2. - PubMed
-
- Stenbaek J, Kalin B, Swedenborg J. Growth of thrombus may be a better predictor of rupture than diameter in patients with abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2000;20:466–469. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases