O-056 - (PHOSPHO)PROTEOMIC SCREEN TO INVESTIGATE THE UNDERLYING MECHANISM OF ALTERED IN VITRO CONTRACTILITY OF VASCULAR SMOOTH MUSCLE CELLS DERIVED FROM ABDOMINAL AORTIC ANEURYSM PATIENTS

TOPIC:
Abdominal Aortic Aneurysms
AUTHORS:
Rombouts K. (Amsterdam UMC, location VUmc ~ Amsterdam ~ Netherlands) , Van Merrienboer T. (Amsterdam UMC, location VUmc ~ Amsterdam ~ Netherlands) , Bogunovic N. (Amsterdam UMC, location VUmc ~ Amsterdam ~ Netherlands) , Van Der Velden J. (Amsterdam UMC, location VUmc ~ Amsterdam ~ Netherlands) , Yeung K.K. (Amsterdam UMC, location VUmc ~ Amsterdam ~ Netherlands)
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 to non-pathologic vSMC, and to find the underlying mechanism of altered in vitro contractility of vSMC derived from AAA patients.
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 to 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.
References:
This project is funded by the Dutch Heart foundation, Dekkerbeurs 2019T065 Senior clinical scientist grant.
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