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Glycoxydation promotes vascular damage via MAPK-ERK/JNK pathways
Filomena de Nigris1, Monica Rienzo, Marcella Sessa
1Department of General Pathology, U.O.C. Immunohematology, and Excellence Research Centre on Cardiovascular Disease, 1st School of Medicine, Second University of Naples, Naples, Italy.
Journal of Cellular Physiology
|February 15, 2012
Summary
Glycated and oxidized LDL (glc-oxLDL) promote foam cell formation by activating MAPK/JNK pathways. This study reveals that these pathways are crucial in glycoxidation-induced vascular damage, impacting both diabetic and euglycemic individuals.
Area of Science:
- Cardiovascular Biology
- Molecular Signaling
- Atherosclerosis Research
Background:
- Oxidized and glycated LDL (glc-oxLDL) contribute to foam cell formation.
- MAPK/JNK signaling pathways are implicated in cellular responses to stress.
Purpose of the Study:
- To investigate the impact of glc-oxLDL on MAPK-ERK and JNK signaling.
- To elucidate the role of MAPK/JNK pathways in glc-oxLDL-induced vascular damage.
Main Methods:
- Human coronary smooth muscle cells were treated with glc-oxLDL.
- Experiments involved analyzing MAPK/JNK signaling and AP-1 complex activation.
- In vivo studies utilized apolipoprotein E knockout (ApoE(-/-)) mice.
Main Results:
- Glc-oxLDL activated MAPK/JNK signaling pathways and the AP-1 complex.
- Tumor necrosis factor-α increased JNK phosphorylation in coronary arterioles.
- Diabetic ApoE(-/-) mice showed increased foam cell formation correlating with JNK and MKK4 phosphorylation.
Conclusions:
- MAPK-ERK/JNK pathways are involved in vascular damage induced by glycoxidation.
- These findings highlight a mechanism linking LDL modification to atherosclerosis progression.
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