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Updated: Jun 14, 2025
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
GP VI-Mediated Platelet Activation and Procoagulant Activity Aggravate Inflammation and Aortic Wall Remodeling in
Tobias Feige1, Agnes Bosbach1, Kim J Krott1
1Department of Vascular and Endovascular Surgery (T.F., A.B., K.J.K., J.M., J.O., E.K., I.K., N.S., W.I., M.U.W., H.S., M.E.), University Hospital Duesseldorf, Heinrich-Heine University, Germany.
Insights
Platelet glycoprotein VI (GP VI) deficiency protects against abdominal aortic aneurysm (AAA) development and progression by reducing inflammation and improving aortic wall remodeling. Targeting GP VI may offer a novel antiplatelet therapy for AAA patients.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Platelet Biology
Background:
- Abdominal aortic aneurysm (AAA) is a lethal, atherosclerosis-related disease characterized by aortic dilatation and inflammation.
- Platelet activation and procoagulant activity are critical in AAA pathogenesis, potentially triggering disease development.
- The role of platelet glycoprotein (GP) VI in AAA initiation and progression requires further investigation.
Purpose of the Study:
- To investigate the impact of the major platelet collagen receptor, GP VI, on the pathophysiological processes underlying AAA.
- To evaluate the potential of GP VI as a therapeutic target for AAA.
Main Methods:
- Experimental AAA induction in mice using porcine pancreatic elastase (PPE).
- Genetic deletion of GP VI in mice to assess its protective effects.
- Analysis of aortic wall inflammation, remodeling markers, and cell apoptosis.
- Measurement of plasma levels of soluble GP VI, fibrin, matrix metalloproteinases (MMPs), and osteopontin (OPN) in patients with AAA.
Main Results:
- Genetic deletion of GP VI protected mice against AAA development, reducing aortic diameter expansion and aneurysm incidence.
- GP VI deficiency led to decreased aortic wall inflammation, characterized by reduced neutrophil and platelet infiltration.
- Absence of GP VI improved aortic wall remodeling, with reduced MMP-2/9 and OPN levels, enhanced α-SMA content, and decreased apoptosis.
- Elevated intima/media thickness and elastin content were observed in GP VI-deficient mice.
- Soluble GP VI and fibrin levels in patients with AAA may serve as potential early detection biomarkers.
Conclusions:
- GP VI plays a significant role in AAA initiation and progression.
- Targeting GP VI with antiplatelet therapy could be a promising strategy to reduce AAA development and progression.
- GP VI-targeted therapy may protect patients with AAA from aortic rupture.
Background:
Platelets play an important role in cardiovascular and cerebrovascular diseases. Abdominal aortic aneurysm (AAA) is a highly lethal, atherosclerosis-related disease with characteristic features of progressive dilatation of the abdominal aorta and degradation of the vessel wall, accompanied by chronic inflammation. Platelet activation and procoagulant activity play a decisive role in the AAA pathology as they might trigger AAA development in both mice and humans.
Methods:
The present study investigated the impact of the major platelet collagen receptor GP (platelet glycoprotein) VI in pathophysiological processes underlying AAA initiation and progression. For experimental AAA induction in mice, PPE (porcine pancreatic elastase) and the external PPE model were used.
Results:
Genetic deletion of GP VI offered protection of mice against aortic diameter expansion in experimental AAA. Mechanistically, GP VI deficiency resulted in decreased inflammation with reduced infiltration of neutrophils and platelets into the aortic wall. Furthermore, remodeling of the aortic wall was improved in the absence of GP VI, as indicated by reduced MMP (matrix metalloproteinase)-2/9 and OPN (osteopontin) plasma levels and an enhanced α-SMA (α-smooth muscle actin) content within the aortic wall, accompanied by reduced cell apoptosis. Consequently, an elevation in intima/media thickness and elastin content was observed in GP VI-deficient PPE mice, resulting in a significantly reduced aortic diameter expansion and reduced aneurysm incidence. In patients with AAA, enhanced plasma levels of soluble GP VI and fibrin, as well as fibrin accumulation within the intraluminal thrombus might serve as new biomarkers to detect AAA early. Moreover, we hypothesize that GP VI might play a role in procoagulant activity and thrombus stabilization via binding to fibrin.
Conclusions:
In conclusion, our results emphasize the potential need for a GP VI-targeted antiplatelet therapy to reduce AAA initiation and progression, as well as to protect patients with AAA from aortic rupture.
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