CEEPC/IPM/CMSC - Abstrakt prezentace

(CEEPC/IPM/CMSC 2022 - FrP-20)
Residual hyperlipidemic stress under lipid lowering treatment may lead toward irreversible NAFLD

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

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

Abstrakt

Background: Nonalcoholic fatty liver disease (NAFLD) includes a range of progressive disorders caused by excess lipids accumulation in the liver leading to hepatic steatosis and eventually fibrosis. Herein, we aim to identify the main signaling pathways and liver proteome alterations induced by hypercholesterolemia in an animal atherosclerotic model.
Methods: Using high-performance mass spectrometry, the effect of combined lipid lowering drugs (statins and anti-PCSK9 monoclonal antibody) were used after the interruption of the hypercholesterolemic diet in an experimental rabbit model to identify potential mediators, such as alarmins, responsible for the irreversible NAFLD build up under the hyperlipidemic sustained stress.
Results: The proteomic analysis revealed a number of differentially abundant proteins associated with Fatty acids degradation, Glycolysis / Gluconeogenesis and Non-alcoholic fatty liver disease. The mitochondrial dysfunction indicated alteration at the mitochondrial respiratory chain level and downregulation of NADH ubiquinone oxidoreductase, while the majority cytochrome expressions (cytochrome P4502E1, cytochrome b5, cytochrome c) are upregulated under lipid lowering treatment. The long term hyperlipidemic stress even under low fat diet and lipid lowering treatment is accompanied by alarmins release (annexins, galactins, HSPs, HMGB1, S100 proteins, calreticulin, fibronectin) that generate local inflammation and induced liver steatosis and aggressive fibrosis (by high abundance of galectin 3, fibronectin and calreticulin).
Conclusion: The novel knowledge uncovered by the present study are related to the residual effects of hyperlipidemic stress under the consistent combined lipid lowering treatment (statin and inhibitor of PCSK9).

* 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.


Partneři společnosti

LabRules LCMS LabRules GCMS

Partneři

Bruker HPST Merck Pragolab Amedis EastPort Shimadzu Waters