CEEPC/IPM/CMSC - Abstrakt prezentace

(CEEPC/IPM/CMSC 2022 - FrP-28)
Arterial Vessel Wall Proteome Alteration Involved in the Regulation of Cell Death Mechanisms in Atherosclerosis

Elena Uyy 1, Viorel Iulian Suica 1, Raluca Maria Boteanu 1, Luminita Ivan 1, Felicia Antohe 1 *

  1. Proteomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Romania

Abstrakt

Background. Atherosclerosis is an inflammatory lipid disease of the arterial vessel wall in which the balance between the predominant cell death mechanisms plays a critical role in dictating the clinical outcome. Unlike the immunologically silent apoptosis, non-apoptotic regulated cell death (necroptosis and ferroptosis) is a process in which affected cells release damage-associated molecular patterns (DAMPs) molecules, which can initiate and perpetuate a non-infectious inflammatory response in arterial wall.
Hypothesis. We hypothesize that DAMPs and non-apoptotic regulated cell death processes are critical players of artery plaque progression with inadequate response to lipid-lowering treatment.
Aim. We aimed to uncover the silent mechanisms that govern the existing residual risk of cardiovascular-related mortality in an experimental hyperlipidemic and hyperglycemic animal model.
Methodology. The study was conducted using proteomic and genomic approaches on the ascending aorta of control and hyperlipidemic and hyperglycemic rabbits with/without lipid-lowering treatment.
Results All animals, except controls, presented hyperglycemia, numerous heterogeneous atherosclerotic arterial lesions, exhibited a high concentration of serum lipid parameters and increased lipid peroxidation oxidative stress markers. The shotgun proteomic analyses revealed that the aortic tissue level of DAMPs and proteins implicated in necroptosis and ferroptosis were significantly upregulated by the hyperlipidemic stress and some of them did not respond to lipid-lowering treatment.
Conclusion. These proteins could play a key role in the vascular disease silent evolution and may possess an unexplored therapeutic potential.

* Korespondující autor: felicia.antohe@icbp.ro

Poděkování:

Romanian Academy, CCCDI-UEFISCDI project COFUND-ERA-CVD-XploreCAD, within PNCDI III and grants from the MRID CNCS - UEFISCDI, PN-III-P4-PCE-2021-1344 and PN-III-P1-1.1-TE-2021-1161 within PNCDI III.


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