Glycoxydation promotes vascular damage Via MAPK-ERK/JNK pathways

• Published in: Journal of cellular physiology Vol. 227; no. 11; pp. 3639 - 3647
• Main Authors: de Nigris, Filomena, Rienzo, Monica, Sessa, Marcella, Infante, Teresa, Cesario, Elena, Ignarro, Louis J., Al-Omran, Mohammed, Giordano, Antonio, Palinski, Wulf, Napoli, Claudio
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2012
• Subjects: Animals; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Cells, Cultured; Coronary Vessels - cytology; Coronary Vessels - metabolism; Diabetes Mellitus, Experimental; Foam Cells - cytology; Foam Cells - metabolism; Humans; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Macrophages, Peritoneal - metabolism; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - genetics; Mice; Mitogen-Activated Protein Kinase Kinases - drug effects; Mitogen-Activated Protein Kinase Kinases - genetics; Muscle, Smooth, Vascular - cytology; Oxidation-Reduction; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.24070

Oxidation and glycation enhance foam cell formation via MAPK/JNK in euglycemic and diabetic subjects. Here, we investigated the effects of glycated and oxidized LDL (glc‐oxLDL) on MAPK‐ERK and JNK signaling pathways using human coronary smooth muscle cells. Glc‐oxLDL induced a broad cascade of MAPK/JNK‐dependent signaling transduction pathways and the AP‐1 complex. In glc‐oxLDL treated coronary arterioles, tumor necrosis factor (TNF) α increased JNK phosphorylation, whereas protein kinase inhibitor dimethylaminopurine (DMAP) prevented the TNF‐induced increase in JNK phosphorylation. The role of MKK4 and JNK were then investigated in vivo, using apolipoprotein E knockout (ApoE−/−) mice. Peritoneal macrophages, isolated from spontaneously hyperlipidemic but euglycemic mice showed increases in both proteins and phosphorylated proteins. Compared to streptozotocin‐treated diabetic C57BL6 and nondiabetic C57BL6 Wt mice, in streptozotocin‐diabetic ApoE−/− mice, the increment of foam cell formation corresponded to an increment of phosphorylation of JNK1, JNK2, and MMK4. Thus, we provide a first line of evidence that MAPK‐ERK/JNK pathways are involved in vascular damage induced by glycoxidation. J. Cell. Physiol. 227: 3639–3647, 2012. © 2012 Wiley Periodicals, Inc.