Characterizing lipoprotein profiles in coronary atherosclerosis development through quantitative lipidomics and...

Lipoproteins, synthesized in the liver and secreted into the bloodstream, play a central role in lipid transport. Although their quality affects cardiovascular outcomes, conventional markers do not fully explain the disease risk. We characterized the lipoprotein composition during coronary atherosclerosis progression in myocardial infarction-prone rabbits, which consistently develop severe aortic lesions but show variable coronary stenosis at 20 months. This variation allowed for the exploration of coronary-specific factors that are often masked by other models. Using quantitative lipidomics and proteomics, we profiled 237 lipids and four apolipoproteins in lipoproteins every four months. Coronary severity was positively correlated with long-chain saturated ceramide levels in very-low- and low-density lipoprotein particles, specifically at eight months, reflecting an early disease stage. This correlation was independent of apolipoproteins and classical risk factors, such as cholesterol and triacylglycerol. Network analysis revealed that lipid class-specific clusters were associated with disease severity. This unbiased multi-omics approach provides novel insights into the contribution of lipoprotein composition to coronary atherosclerosis.