Cardiac Alarmins as Residual Risk Markers of Atherosclerosis under Hypolipidemic Therapy

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11174
• Main Authors: Suica, Viorel I., Uyy, Elena, Ivan, Luminita, Boteanu, Raluca M., Cerveanu-Hogas, Aurel, Hansen, Rune, Antohe, Felicia
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2022; MDPI
• Subjects: alarmins; Animals; Arteriosclerosis; Atherosclerosis; Atorvastatin; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Coronary vessels; Diet; Heat shock proteins; High fat diet; HMGB1 protein; Hyperlipidemia; Lipids; Lipoproteins; Lysates; Mass spectrometry; Mass spectroscopy; Metabolism; Mutation; Neutrophils; Plasma; Proteins; proteomics; Rabbits; residual risk; Risk analysis; Risk factors; Scientific imaging; siRNA; Statins; Triglycerides; Ventricle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911174

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.