Activator protein-1 (AP-1) signalling in human atherosclerosis: results of a systematic evaluation and intervention study
| Autor: | J. Hajo van Bockel, Pum A. le Haen, C. Arnoud Meijer, Jaap F. Hamming, Jan H.N. Lindeman, Rogier A. van Dijk, Mitsuhisa Hira |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology SMC smooth muscle cell ICAM-1 intercellular adhesion molecule-1 vWF von Willebrand factor Fibrinogen Systemic inflammation activator protein 1 (AP-1) Phosphorylation Aorta Cross-Over Studies biology clinical trial General Medicine Middle Aged MCP-1 monocyte chemoattractant protein-1 Immunohistochemistry NTG nitroglycerine C-Reactive Protein PAI-1 plasminogen activator inhibitor-1 Disease Progression Female Animal studies medicine.symptom Inflammation Mediators AP-1 activator protein-1 medicine.drug Signal Transduction Research Article medicine.medical_specialty HDL high-density lipoprotein S9 CVD cardiovascular disease Lesion Peripheral Arterial Disease Von Willebrand factor Double-Blind Method PAD peripheral arterial disease medicine.artery medicine Humans Aged AAA abdominal aortic aneurysm doxycycline C-reactive protein JNK Mitogen-Activated Protein Kinases Atherosclerosis IL interleukin Transcription Factor AP-1 hs-CRP high-sensitivity C-reactive protein inflammation biology.protein Plasminogen activator Biomarkers |
| Zdroj: | Clinical Science (London, England : 1979) Clinical Science, 122(9), 421-8 |
| Popis: | Animal studies implicate the AP-1 (activator protein-1) pro-inflammatory pathway as a promising target in the treatment of atherosclerotic disease. It is, however, unclear whether these observations apply to human atherosclerosis. Therefore we evaluated the profile of AP-1 activation through histological analysis and tested the potential benefit of AP-1 inhibition in a clinical trial. AP-1 activation was quantified by phospho-c-Jun nuclear translocation (immunohistochemistry) on a biobank of aortic wall samples from organ donors. The effect of AP-1 inhibition on vascular parameters was tested through a double blind placebo-controlled cross-over study of 28 days doxycycline or placebo in patients with symptomatic peripheral artery disease. Vascular function was assessed by brachial dilation as well as by plasma samples analysed for hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), IL-8, ICAM-1 (intercellular adhesion molecule-1), vWF (von Willebrand factor), MCP-1 (monocyte chemoattractant protein-1), PAI-1 (plasminogen activator inhibitor-1) and fibrinogen. Histological evaluation of human atherosclerosis showed minimal AP-1 activation in non-diseased arterial wall (i.e. vessel wall without any signs of atherosclerotic disease). A gradual increase of AP-1 activation was found in non-progressive and progressive phases of atherosclerosis respectively (P |
| Databáze: | OpenAIRE |
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