Open Access
CC BY 4.0 · Aorta (Stamford) 2022; 10(S 01): A1-A56
DOI: 10.1055/s-0042-1750922
Presentation Abstracts

(PHOSPHO) Proteomic Screen to Investigate The Underlying Mechanism of Altered in Vitro Contractility of Vascular Smooth Muscle Cells Derived from Abdominal Aortic Aneurysm Patients

Karlijn Rombouts
1   Amsterdam University Medical Center, VU University Medical Center, Amsterdam, The Netherlands
,
Tara van Merrienboer
1   Amsterdam University Medical Center, VU University Medical Center, Amsterdam, The Netherlands
,
Natalija Bogunovic
1   Amsterdam University Medical Center, VU University Medical Center, Amsterdam, The Netherlands
,
Jolanda van der Velden
1   Amsterdam University Medical Center, VU University Medical Center, Amsterdam, The Netherlands
,
Kak Khee Yeung
1   Amsterdam University Medical Center, VU University Medical Center, Amsterdam, The Netherlands
› Author Affiliations
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    Introduction: Abdominal aortic aneurysms (AAA) are defined as a progressive weakening of the aortic wall, leading to gradual dilatation. We hypothesize that dysfunction of vascular smooth muscle cells (vSMC), the major cell type within the aortic wall, plays a paramount role in AAA pathophysiology. The aim of this study is to investigate in vitro contractility of human AAA vSMC compared with non-pathologic vSMC.

    Methods: Contractility of vSMC isolated from biopsies from AAA patients (n = 39) and controls (n = 18, vSMC derived from non-dilated aortas of post-mortem heart beating kidney transplant donors) was measured using Electric Cell-substrate Impedance Sensor. vSMC were stimulated with ionomycin (Ca2+ ionophore which induces a contractile response in adherent vSMC by the influx of extracellular Ca2+). To investigate the underlying mechanism of impaired vSMC contractility and the involved proteins a (phospho)proteomics analysis was performed in vSMC lysates of AAA patients (n = 24) and controls (n = 8).

    Results: vSMC contractility of AAA patients showed more variability compared with control vSMC. To define normal vSMC contractility range, mean contractility including ± 2 standard deviations (2SD) of the control cell lines was determined (83,51% ± 6,48%). AAA patients? vSMC were divided into subgroups based on this control vSMC contractility range (AAA-Low contracting: mean: 70,63%, SD: 5,51% (n = 8); AAA-Normal contracting: mean: 83.69%, SD: 3.35% (n = 22); AAA-High contracting: mean: 91.72%, SD: 1.22% (n = 9)). The differences in vSMC contraction in AAA patients is correlated to changes in extracellular matrix and cell adhesion proteins and by pathways related to energy production.

    Conclusion: vSMC contractility is altered in certain subgroups of AAA patients and might therefore play a role in AAA pathophysiology. Finding proteins involved in altered vSMC contractility is of clinical importance since it can represent potential targets for novel non-invasive treatments for prevention and/or stabilization of AAA.

    This project is funded by the Dutch Heart foundation, Dekkerbeurs 2019T065 Senior clinical scientist grant.

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    Fig. 1 Vascular Smooth Muscle Cell contraction of Abdominal Aortic Aneurysm patients and controls. Dotted lines represent the ± 2 standard deviations range from the control contractility. Abdominal Aortic Aneurysm patients are subdived in to low, normal and high contraction based on this range.
    Zoom
    Fig. 2 Heat map of proteomics screen from Vascular Smooth Muscle Cells from Abdominal Aortic Aneurysm patients with high and low contraction.

     

    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    10 June 2022

    © 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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    Zoom
    Fig. 1 Vascular Smooth Muscle Cell contraction of Abdominal Aortic Aneurysm patients and controls. Dotted lines represent the ± 2 standard deviations range from the control contractility. Abdominal Aortic Aneurysm patients are subdived in to low, normal and high contraction based on this range.
    Zoom
    Fig. 2 Heat map of proteomics screen from Vascular Smooth Muscle Cells from Abdominal Aortic Aneurysm patients with high and low contraction.