Mapping the Lipidome in Atherosclerosis

Cardiovascular diseases are the leading cause of death worldwide, responsible for an estimated 20.5 million deaths in 2021. Of these, 85% were due to myocardial infarctions and strokes, primarily caused by atherosclerosis. Atherosclerosis is an arterial disease in which plaque build-up narrows the arteries over time. Plaque rupture exposes its contents to the bloodstream, triggering thrombus formation that can obstruct blood flow, leading to cardiovascular events. Early detection and risk stratification are crucial to prevent plaque rupture and determine appropriate interventions.
This thesis explores the lipid composition of atherosclerotic plaques to understand their role in disease progression and instability. Using advanced mass spectrometry imaging (MSI) techniques, combined with histology and lipidomics, we identified key lipid species, such as sphingomyelins, ceramides, cholesteryl esters, and phospholipids, associated with necrosis, calcification, and inflammation in human carotid plaques and coronary plaques from a swine model. These findings have advanced our understanding of the complex lipid-mediated mechanisms underlying atherosclerosis.