Low density lipoproteins (LDL)'s modifications in the vascular wall, by oxidation, glycation, glycoxidation or aggregation, plays a key-role in the early stages of atherogenesis, characterized by the accumulation of foam cells, the formation of fatty streaks and the proinflammatory immune response.

During the progression of atherosclerosis, oxidized lipids accumulate in the necrotico-lipid core, and participate in the development of lesions towards more advanced stages. Oxidized lipids promote local inflammatory responses, stimulate the migration and proliferation of smooth muscle cells, as well as the extracellular matrix production and plaque remodeling. These lipids are involved in angiogenesis, induce apoptosis and contribute to vascular aging. Oxidized lipid properties depend on their local concentration, their nature (oxidized phospholipids, oxysterols, aldehydes…), their uptake by scavenger receptors (CD36, LOX-1, SRA...) that differ as function of the cell type. Finally, oxidized lipids can generate cellular responses (oxidative stress, protease secretion, cellular dysfunction, apoptosis ...), which contribute to fragilize the lesions, promote plaque erosion or rupture and finally lead to athero-thrombosis events.

Our team "Lipids, Peroxidation, Signaling in Vascular Diseases" involves researchers, clinicians and technicians aiming at better understanding the mechanisms involved in plaque progression and instability, and particularly the factors related to LDL modification and oxidation. In our previous studies, we have deciphered some atherogenic properties of oxidized LDL and lipids, such as the mechanisms implicated in the balance between cell survival and death, that conditions the fate of vascular cells. These pathways include the ceramide/sphingosine-1-phosphate rheostat, which promotes the survival, migration and proliferation of smooth muscle cells, and constitutes a key mechanism (with VEGF) for the development of neoangiogenesis, the endoplasmic reticulum stress implicated in cell survival and apoptosis, the cytosolic calcium dysregulation, which plays an essential role in cell death induced by oxidized LDL, the presence of antioxidant and antiapoptotic defense systems, or the autophagy and mitophagic pathways involved in survival and efferocytosis. The modification of cellular proteins by aldehydes generated during lipid peroxidation, progressively alters these protective functions and contributes to cellular dysfunction and apoptosis.

Our objectives are to i / identify and characterize the role of oxidized lipids and modified LDL in the progression of atherosclerotic lesions, and more precisely the mechanisms of neoangiogenesis, vascular aging, calcification of advanced plaques, or the protective role of autophagy and mitophagy in the fate of the plaque (ii) developing innovative computational vascular medical imaging techniques for visualizing vascular hemodynamics and wall shear stress, and (iii) identifying new non-invasive biomarkers for the coronary patient follow-up.