Glycoxidation of low-density lipoprotein promotes multiple apoptotic pathways and NFkappaB activation in human coronary cells.
Apoptosis of arterial cells induced by oxidized low-density lipoprotein (oxLDL) is thought to contribute to the progression of vascular dysfunction and atherogenesis. It is well established that diabetes mellitus is accompanied by both glycosylation and oxidation LDL, but the biological effects of these modified lipoproteins are poorly understood. We demonstrate here that glycosylated oxLDL (glc-oxLDL) promotes apoptotic signaling in human coronary smooth muscle cells. This was associated by a decrease of the antiapoptotic protein Bcl-2, an increase of the pro-apoptotic protein Bax, and activation of caspase 3. Glc-oxLDL also activated NFK: B and decreased IK: B, these effects were more pronounced than those achieved with oxLDL. Our study shows that glc-oxLDL influences a broad cascade of signaling transduction pathways, which may not only result in apoptosis, but also could affect NFkappaB in human coronary cells. This cascade of events may influence the evolution of atherogenesis and vascular complications in diabetic patients.
de Nigris
Filomena
F
Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, II University of Naples, Via Luigi de Crecchio 7, Naples 80138, Italy.
Gallo
Lidia
L
Sica
Vincenzo
V
Napoli
Claudio
C
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C099252:oxidized low density lipoprotein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases