The NF-kappaB and IkappaB system in injured arteries. 1998

V Lindner
Center for Molecular Medicine, Maine Medical Center Research Institute, South Portland, ME 04106, USA. lindnv@poa.mmc.org

Activation of endothelial cells and dedifferentiation of smooth muscle cells (SMC) are events in the development of vascular disease. The NF-kappaB transcription factor family and its inhibitory proteins (IkappaB) have been implicated in regulating the expression of genes associated with the concomitant inflammatory response. To determine the role of the NF-kappaB/IkappaB system in vivo, the present study used the balloon catheter injury model in the rat carotid artery. Immunoblotting revealed that higher levels of the NF-kappaB family members p50, p52, p65, c-Rel, and RelB were expressed in injured arteries during lesion formation compared to normal vessels. Using electromobility shift assays, low levels of constitutively activated NF-kappaB were seen in normal carotid arteries and an induction occurred during times of rapid SMC proliferation. Furthermore, immediately after injury, the levels of the inhibitor proteins IkappaB alpha, IkappaB beta, and p105 were dramatically reduced. Consistent with the activation of NF-kappaB, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) were induced in SMC and endothelial cells as early as 4 h after injury and this was accompanied by adhesion of monocytes/macrophages. SMC forming a pseudoendothelium in chronically denuded vessels continued to express high levels of VCAM-1 and MCP-1, thus perpetuating the inflammatory response. These findings link the activation of NF-kappaB to the inflammatory response and to intimal lesion formation following vascular injury.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000072000 NF-KappaB Inhibitor alpha An I-kappa B protein that inhibits the activity of dimeric NF-KAPPA B P50-REL complexes, sequesters transcription factor NF-kappaB as an inactive complex in the cytoplasm; and prevents NF-kappaB nuclear translocation and DNA binding. I Kappa B-alpha Protein,IKappaB-alpha,IKappaBalpha,Major Histocompatibility Complex Enhancer-Binding Protein MAD3,p40 Protein (IKappaB-alpha),I Kappa B alpha Protein,IKappaB alpha,Inhibitor alpha, NF-KappaB,Major Histocompatibility Complex Enhancer Binding Protein MAD3,NF KappaB Inhibitor alpha,alpha, NF-KappaB Inhibitor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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