PB1409 - The impact of platelets on inflammation and extracellular matrix remodelling in abdominal aortic aneurysm formation

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Agnes Ehrenberg, M.Sc. (she/her/hers)

PhD student
Department of Vascular and Endovascular Surgery
Düsseldorf, Nordrhein-Westfalen, Germany

Co-Author(s)

Tobias Feige, M.Sc. (he/him/his)

Ph.D. student
Department of Vascular and Endovascular Surgery, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Duesseldorf, Nordrhein-Westfalen, Germany
KK

Kim-Jürgen Krott

PostDoc
Clinic of Vascular and Endovascular Surgery,University Clinic of the Heinrich-Heine-University, Düsseldorf, Germany
40225 Düsseldorf, Nordrhein-Westfalen, Germany
RH

Rhee Hyun

MD
Clinic of endovascular surgery
40225 Düsseldorf, Nordrhein-Westfalen, Germany
MJ

Mulorz Joscha

Dr. med.
Clinic of endovascular surgery
40225 Düsseldorf, Nordrhein-Westfalen, Germany
MW

Markus Wagenhäuser

PD Dr.
Clinic of endovascular surgery
40225 Düsseldorf, Nordrhein-Westfalen, Germany
HS

Hubert Schelzig

Univ.- Prof. Dr. med
Clinic of endovascular surgery
40225 Düsseldorf, Nordrhein-Westfalen, Germany
ME

Margitta Elvers

Professor
Clinic for Vascular- and Endovascular Surgery, University Clinic of the Heinrich-Heine- University Düsseldorf, Düsseldorf, Germany.
Duesseldorf, Nordrhein-Westfalen, Germany

Background: Abdominal aortic aneurysm (AAA) is characterised by the dilatation of the abdominal aorta. Additional hallmarks of AAA development are extracellular matrix (ECM) degradation, enhanced immune cell infiltration, vascular smooth muscle cell (VSMC) apoptosis, and the formation of a platelet-rich intraluminal thrombus (ILT). In recent studies, it was shown that the release of pro-inflammatory cytokines and growth factors by platelets, as well as the direct cell-cell interaction of platelets with inflammatory cells substantially alter cell signalling cascades of resident and non-resident cells.

Aims: However, the impact of platelets on inflammation and matrix degradation in AAA development is still poorly understood.

Methods: Porcine pancreatic elastase (PPE) model, 2D-ultrasound measurement, immunfluorescence staining, cell culture, qRT-PCR.

Results: Platelet-depletion in PPE operated mice results in a decreased aortic diameter and preserved pulse wave velocity, compared to non-depleted PPE mice. Moreover, aortic tissue of platelet-depleted PPE mice reveals reduced stiffness-related gene expression of Osteopontin, matrix-metalloproteinases and collagen , accompanied by an altered expression of pro- and anti-inflammatory cytokines. Consequently, platelet-depletion results in a reduced recruitment of macrophages into the developing aneurysm in PPE operated mice. These results indicate that platelets contribute to local inflammation by modulating macrophage recruitment to the aortic wall. In comparison to these, treatment of M1 macrophages with the supernatant of resting and activated platelets leads to enhanced SPP1 and MMP9 gene expression, accompanied by an increased expression of the pro-inflammatory cytokines. In patients with AAA, platelet activation and pro-coagulant activity was elevated. Platelets and OPN were detected in the vessel wall and in the ILT of AAA patients. OPN co-localizes with platelets suggesting a potential role of OPN for the recruitment of platelets.

Conclusion(s): In conclusion, platelets directly contribute to AAA formation and progression by altering inflammation and ECM remodelling, what supports the potential relevance of anti-platelet therapy to reduce AAA progression and rupture.