Nanoparticle-Enabled Plasma Proteomics of Experimental Atherosclerosis in Mice

Dyslipidemia, marked by elevated low-density lipoprotein cholesterol, is a major risk factor for coronary heart disease. Mouse experimental systems, such as Ldlr^-/- mice that develop atherosclerosis and metabolic disorders when fed a high-fat diet (HFD), are crucial for studying disease mechanisms and identifying potential biomarkers. Using recent nanoparticle-dependent enrichment of plasma proteins and mass spectrometry, we quantified 5,080 plasma proteins from Ldlr^-/- mice fed a chow or HFD for 3 or 6 months. Proteins with sustained enrichment in HFD were indicative of liver cell subtypes, whereas proteins that increased from 3 to 6 months were indicative of inflammation and endothelial activation. Proteins/genes from human cardiovascular genomic and proteomic studies were also detected in the plasma and aorta including MMP12, LPL, and HP that increased with HFD. These data provide many avenues for understanding disease pathology and uncovering novel molecular contributors to cardiovascular diseases.