PB0595 - The profile of contact activation system proteins in human abdominal aortic aneurysm plasma- and tissue samples

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Stephanie Thuy Duong Pham, MSc (she/her/hers)

PhD student
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Odense C, Syddanmark, Denmark

Co-Author(s)

JS

Jes Sanddal Lindholt

Professor
Department of Cardiac, Thoracic, and Vascular Surgery, Odense University Hospital, Odense, Denmark
Odense C, Syddanmark, Denmark
JM

Jose Luis Martin-Ventura

Professor
IIS-Fundación Jiménez-Díaz, Universidad Autonoma de Madrid; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Madrid, Madrid, Spain
EB

Else-Marie Bladbjerg

Professor
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark.
Esbjerg, Syddanmark, Denmark
Katrine Pilely, PhD (she/her/hers)

Postdoc
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Odense, Syddanmark, Denmark
YP

Yaseelan Palarasah, MSc, PhD

Associate professor
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
Odense, Syddanmark, Denmark

Background: The contact activation system (CAS) is a highly regulated system that comprises promotion of coagulation and inflammation. It involves the plasma proteins FXII, prekallikrein (PK), and H-kininogen (HK). Previous studies indicated an association between PK and the disease abdominal aortic aneurysm (AAA). AAA is a life-threatening and often asymptomatic disease. Rupture of AAA is associated with severe internal bleeding and high mortality rates. Currently, no medical treatment exists for the disease. The lack of studies demonstrating a detailed disease model of the CAS in AAA emphasizes the need for investigating the CAS in relation to AAA.

Aims: The aim of this study is to investigate the CAS in human AAA-plasma and -tissue using new methods focusing on measurements of the total capacity of the CAS.

Methods: We have recently generated cleaved HK (cHK) specific mouse monoclonal antibodies (mAbs) using a peptide, corresponding to the plasma kallikrein cleavage site on HK, as immunogen. Using this cHK-assay, together with already established in-house FXII-, PK-, and intact HK-assays, we were able to measure CAS proteins in human AAA-samples. The CAS proteins were assessed in plasma samples from AAA-patients (n=53) and compared with plasma samples from coronary artery bypass grafting (CABG)-patients (n=30). Furthermore, the presence of CAS was determined in human tissue samples from AAA-patients (n=51) and healthy individuals (n=36).

Results: Our results showed increased plasma levels of cHK and intact HK in AAA-patients compared with CABG-patients, while showing no differences in plasma FXII- and PK-levels. Furthermore, we found increased levels of all the CAS proteins FXII, PK, HK, and cHK in the AAA-tissue samples compared to healthy individuals.

Conclusion(s): The increased level of the CAS activation product cHK suggests that CAS is activated in AAA, and the presence of CAS proteins in the AAA-tissue samples indicates that the CAS may play an important role in AAA locally.