title: Requirement of JNK1 for endothelial cell injury in atherogenesis.
abstract: OBJECTIVE
  The c-Jun N-terminal kinase (JNK) family regulates fundamental physiological processes including apoptosis and metabolism. Although JNK2 is known to promote foam cell formation during atherosclerosis, the potential role of JNK1 is uncertain. We examined the potential influence of JNK1 and its negative regulator, MAP kinase phosphatase-1 (MKP-1), on endothelial cell (EC) injury and early lesion formation using hypercholesterolemic LDLR(-/-) mice.
  
  
  RESULTS
  To assess the function of JNK1 in early atherogenesis, we measured EC apoptosis and lesion formation in LDLR(-/-) or LDLR(-/-)/JNK1(-/-) mice exposed to a high fat diet for 6 weeks. En face staining using antibodies that recognise active, cleaved caspase-3 (apoptosis) or using Sudan IV (lipid deposition) revealed that genetic deletion of JNK1 reduced EC apoptosis and lesion formation in hypercholesterolemic mice. By contrast, although EC apoptosis was enhanced in LDLR(-/-)/MKP-1(-/-) mice compared to LDLR(-/-) mice, lesion formation was unaltered.
  
  
  CONCLUSIONS
  We conclude that JNK1 is required for EC apoptosis and lipid deposition during early atherogenesis. Thus pharmacological inhibitors of JNK may reduce atherosclerosis by preventing EC injury as well as by influencing foam cell formation.
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Narges
authors: N
authors: Amini
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Joseph J
authors: JJ
authors: Boyle
authors: Department of Cardiovascular Sciences, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, Sheffield, UK.
authors: Britta
authors: B
authors: Moers
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Christina M
authors: CM
authors: Warboys
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Talat H
authors: TH
authors: Malik
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Mustafa
authors: M
authors: Zakkar
authors: Department of Cardiovascular Sciences, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, Sheffield, UK.
authors: Sheila E
authors: SE
authors: Francis
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Justin C
authors: JC
authors: Mason
authors: British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.
authors: Dorian O
authors: DO
authors: Haskard
authors: Department of Cardiovascular Sciences, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, Sheffield, UK. Electronic address: paul.evans@sheffield.ac.uk.
authors: Paul C
authors: PC
authors: Evans
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D059305:Diet, High-Fat; D054638:Dual Specificity Phosphatase 1 / Q000172:deficiency; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000172:deficiency* / Q000378:metabolism
chemical_list: D048055:Mitogen-Activated Protein Kinase 8; D054638:Dual Specificity Phosphatase 1
keywords: Apoptosis; Atherosclerosis; Endothelial cells; MAP kinase phosphatase; c-Jun N-terminal kinase