Signalisation apototique induite par les LDL oxydées Implication dans l’athérosclérose

Inserm U-466 et Laboratoire de biochimie médicale, Institut Louis Bugnard, Faculté de Médecine, Université Paul Sabatier, Toulouse, France. +33-561-32-20-84

^* anesalv@toulouse.inserm.fr

Abstract

The balance between vascular cell proliferation vs apoptosis plays a key role in vessel wall remodeling. Intimal migration and proliferation of smooth muscle cells (SMC), and secretion of extracellular matrix are involved in fibrous cap formation and plaque stability, whereas apoptosis of vascular cells may contribute to the erosion and instability of the plaque leading to its rupture and subsequent thrombus formation. LDL become atherogenic after undergoing oxidation within the vascular wall. Oxidized LDL (oxLDL) and oxidized lipids exhibit complex biological properties involved in endothelial dysfunction, SMC migration and proliferation, inflammation, and apoptosis. Oxidized LDL-induced apoptosis involves the extrinsic propapoptotic pathway (linked to Fas/Fas ligand) in lymphocytes, and the intrinsic mitochondrial apoptotic pathway, involving bcl-2 family members, cytochrome C release, and the terminal executive caspase-3 pathway, as well as the mitochondrial apoptotic factor AIF, in vascular cells. The apoptotic signaling of oxLDL is mediated in part by an intense and sustained rise of cytosolic calcium. The mechanisms regulating the balance between proliferation and apoptosis triggered by oxLDL and their role in vivo in atherosclerotic plaque progression remains to be clarified.