Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Osto, E; Matter, CM; Kouroedov, A; Malinski, T; Bachschmid, M; Camici, GG; Kilic, U; Stallmach, T; Boren, J; Iliceto, S; Lüscher, TF; Cosentino, F.
c-Jun N-terminal kinase 2 deficiency protects against hypercholesterolemia-induced endothelial dysfunction and oxidative stress.
Circulation. 2008; 118(20):2073-80 Doi: 10.1161/CIRCULATIONAHA.108.765032
Web of Science PubMed FullText FullText_MUG

 

Führende Autor*innen der Med Uni Graz
Osto Elena
Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:
BACKGROUND: Hypercholesterolemia-induced endothelial dysfunction due to excessive production of reactive oxygen species is a major trigger of atherogenesis. The c-Jun-N-terminal kinases (JNKs) are activated by oxidative stress and play a key role in atherogenesis and inflammation. We investigated whether JNK2 deletion protects from hypercholesterolemia-induced endothelial dysfunction and oxidative stress. METHODS AND RESULTS: Male JNK2 knockout (JNK2(-/-)) and wild-type (WT) mice (8 weeks old) were fed either a high-cholesterol diet (HCD; 1.25% total cholesterol) or a normal diet for 14 weeks. Aortic lysates of WT mice fed a HCD showed an increase in JNK phosphorylation compared with WT mice fed a normal diet (P<0.05). Endothelium-dependent relaxations to acetylcholine were impaired in WT HCD mice (P<0.05 versus WT normal diet). In contrast, JNK2(-/-) HCD mice did not exhibit endothelial dysfunction (96+/-5% maximal relaxation in response to acetylcholine; P<0.05 versus WT HCD). Endothelium-independent relaxations were identical in all groups. A hypercholesterolemia-induced decrease in nitric oxide (NO) release of endothelial cells was found in WT but not in JNK2(-/-) mice. In parallel, endothelial NO synthase expression was upregulated only in JNK2(-/-) HCD animals, whereas the expression of antioxidant defense systems such as extracellular superoxide dismutase and manganese superoxide dismutase was decreased in WT but not in JNK2(-/-) HCD mice. In contrast to JNK2(-/-) mice, WT HCD displayed an increase in O(2)(-) and ONOO(-) concentrations as well as nitrotyrosine staining and peroxidation. CONCLUSIONS: JNK2 plays a critical role as a mediator of hypercholesterolemia-induced endothelial dysfunction and oxidative stress. Thus, JNK2 may provide a novel target for prevention of vascular disease and atherosclerosis.
Find related publications in this database (using NLM MeSH Indexing)
Acetylcholine - pharmacology
Animals - administration & dosage
Aorta - enzymology
Endothelial Cells - metabolism
Endothelium, Vascular - cytology, drug effects, physiopathology
Enzyme Activation - administration & dosage
Free Radical Scavengers - metabolism
Hypercholesterolemia - metabolism, physiopathology
JNK Mitogen-Activated Protein Kinases - metabolism
Lipids - blood
Male - administration & dosage
Mice - administration & dosage
Mice, Knockout - administration & dosage
Mitogen-Activated Protein Kinase 9 - deficiency, metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Oxidative Stress - administration & dosage
Vasodilation - administration & dosage
Vasodilator Agents - pharmacology

Find related publications in this database (Keywords)
atherosclerosis
endothelium
nitric oxide
JNK kinase
reactive oxygen species
© Med Uni Graz • Impressum