Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Isoda, K; Young, JL; Zirlik, A; MacFarlane, LA; Tsuboi, N; Gerdes, N; Schönbeck, U; Libby, P.
Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells.
ARTERIOSCL THROM VAS. 2006; 26(3): 611-617.
Doi: 10.1161/01.ATV.0000201938.78044.75
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- Co-Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- Metformin may benefit the macrovascular complications of diabetes independently of its conventional hypoglycemic effects. Accumulating evidence suggests that inflammatory processes participate in type 2 diabetes and its atherothrombotic manifestations. Therefore, this study examined the potential action of metformin as an inhibitor of pro-inflammatory responses in human vascular smooth muscle cells (SMCs), macrophages (Mphis), and endothelial cells (ECs). Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis. Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs. Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity. To address the significance of the anti-inflammatory effects of a therapeutically relevant plasma concentration of metformin (20 micromol/L), we conducted experiments in ECs treated with high glucose. Pretreatment with metformin also decreased phosphorylation of Akt and protein kinase C (PKC) in ECs under these conditions. These data suggest that metformin can exert a direct vascular anti-inflammatory effect by inhibiting NF-kappaB through blockade of the PI3K-Akt pathway. The novel anti-inflammatory actions of metformin may explain in part the apparent clinical reduction by metformin of cardiovascular events not fully attributable to its hypoglycemic action.
- Find related publications in this database (using NLM MeSH Indexing)
- Anti-Inflammatory Agents - pharmacology
- Atherosclerosis - drug therapy
- Atherosclerosis - immunology
- Cell Survival - drug effects
- Cells, Cultured -
- Diabetes Mellitus, Type 2 - drug therapy
- Diabetes Mellitus, Type 2 - immunology
- Diabetic Angiopathies - drug therapy
- Diabetic Angiopathies - immunology
- Endothelium, Vascular - cytology
- Endothelium, Vascular - drug effects
- Endothelium, Vascular - immunology
- Glucose - pharmacology
- Humans -
- Hypoglycemic Agents - pharmacology
- Interleukin-1 - antagonists & inhibitors
- Interleukin-1 - metabolism
- Interleukin-6 - metabolism
- Interleukin-8 - metabolism
- Macrophages - cytology
- Macrophages - drug effects
- Macrophages - immunology
- Metformin - pharmacology
- Muscle, Smooth, Vascular - cytology
- Muscle, Smooth, Vascular - drug effects
- Muscle, Smooth, Vascular - immunology
- NF-kappa B - metabolism
- Phosphatidylinositol 3-Kinases - metabolism
- Proto-Oncogene Proteins c-akt - metabolism
- Saphenous Vein - cytology
- Find related publications in this database (Keywords)
- atherosclerosis
- diabetes
- inflammation
- interleukins
- smooth muscle cell