Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/ijms231911174
Keywords
atherosclerosis; alarmins; residual risk; proteomics; mass spectrometry
Funding
- Romanian Academy
- Romanian National Authority for Scientific Research and Innovation, CCCDI-UEFISCDI project COFUND-ERA-CVD-XploreCAD, within PNCDI III
- Ministry of Research, Innovation and Digitization, CNCS-UEFISCDI [PN-III-P1-1.1-TE-2021-1161, PN-III-P4-PCE-2021-1344]
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Increased levels of low-density lipoproteins are the main risk factor in the initiation and progression of atherosclerosis. This study suggests that a specific panel of stress-sensing molecules (alarmins) may indicate the persistence of residual risk in silent atherosclerosis.
Increased levels of low-density lipoproteins are the main risk factor in the initiation and progression of atherosclerosis. Although statin treatment can effectively lower these levels, there is still a residual risk of cardiovascular events. We hypothesize that a specific panel of stress-sensing molecules (alarmins) could indicate the persistence of silent atherosclerosis residual risk. New Zealand White rabbits were divided into: control group (C), a group that received a high-fat diet for twelve weeks (Au), and a treated hyperlipidemic group with a lipid diet for eight weeks followed by a standard diet and hypolipidemic treatment (atorvastatin and PCSK9 siRNA-inhibitor) for four weeks (Asi). Mass spectrometry experiments of left ventricle lysates were complemented by immunologic and genomic studies to corroborate the data. The hyperlipidemic diet determined a general alarmin up-regulation tendency over the C group. A significant spectral abundance increase was measured for specific heat shock proteins, S100 family members, HMGB1, and Annexin A1. The hypolipidemic treatment demonstrated a reversed regulation trend with non-significant spectral alteration over the C group for some of the identified alarmins. Our study highlights the discriminating potential of alarmins in hyperlipidemia or following hypolipidemic treatment. Data are available via ProteomeXchange with identifier PXD035692.
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