Two Distinct Calcium-Dependent Mitochondrial Pathways Are Involved in Oxidized LDL-Induced Apoptosis

摘要: Objective— Oxidized low-density lipoprotein (oxLDL)-induced apoptosis of vascular endothelial cells may contribute to plaque erosion and rupture. We aimed clarify the relationship between oxLDL-induced calcium signal induction apoptotic pathways. Methods Results— Apoptosis was evaluated by biochemical methods, including studies enzyme activities, protein processing, release proapoptotic factors, chromatin cleavage, especially morphological methods that evaluate apoptosis/necrosis SYTO-13/propidium iodide fluorescent labeling. The sustained rise activated 2 distinct calcium-dependent mitochondrial pathways in human microvascular cells. OxLDLs induced calpain activation subsequent Bid cleavage cytochrome C release, which were blocked calpeptin. Cyclosporin-A inhibited possibly inhibiting opening permeability transition pore (mPTP). Calcineurin, another cyclosporin-sensitive step, not implicated, because oxLDLs calcineurin FK-506 treatment ineffective. Cytochrome turn caspase-3 activation. In addition, triggered nuclear translocation apoptosis-inducing factor through a mechanism dependent on but independent calpains, mPTP, caspases. Conclusions— OxLDL-induced involves pathways, first mediated calpain/mPTP/cytochrome C/caspase-3 second factor, is cyclosporin-insensitive caspase-independent.