Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice. 2010

Levent M Akyürek, and Manfred Boehm, and Michelle Olive, and Alex-Xianghua Zhou, and Hong San, and Elizabeth G Nabel
National Human Genome Research Institute and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1), are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21(Cip1) or p27(Kip1) in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE(-/-) aortae, both apoE(-/-)/p21(-/-) and apoE(-/-)/p27(-/-) aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27(Kip1) accelerated plaque formation significantly more than p21(-/-) in apoE(-/-) mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21(Cip1) and p27(Kip1) accelerates atherogenesis in apoE(-/-) mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

UI MeSH Term Description Entries
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004036 Diet, Atherogenic A diet that contributes to the development and acceleration of ATHEROGENESIS. Atherogenic Diet,Atherogenic Diets,Diets, Atherogenic
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
D001011 Aorta The main trunk of the systemic arteries. Aortas
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050197 Atherosclerosis A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA. Atherogenesis,Atherogeneses,Atheroscleroses
D050759 Cyclin-Dependent Kinase Inhibitor p21 A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3. CDK2-Associated Protein 20 kDa,CDKN1 Protein,CDKN1A Protein,Cdk-Interacting Protein 1,Cdk2 Inhibitor Protein,Cell Cycle Regulator p21,Cyclin Kinase Inhibitor p21,Cyclin-Dependent Kinase Inhibitor 1A Protein,Senescent Cell-Derived Inhibitor Protein 1,p21 Cell Cycle Regulator,p21 Cyclin Kinase Inhibitor,CDK2 Associated Protein 20 kDa,Cdk Interacting Protein 1,Cyclin Dependent Kinase Inhibitor 1A Protein,Cyclin Dependent Kinase Inhibitor p21,Senescent Cell Derived Inhibitor Protein 1
D050760 Cyclin-Dependent Kinase Inhibitor p27 A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2. CDK Inhibitor p27,CDKN1B Protein,CDKN4 Protein,Cyclin-Dependent Kinase Inhibitor 1B,p27 CDK Inhibitor,p27 Kip1 Protein,p27Kip1 Protein,CDK Inhibitor, p27,Cyclin Dependent Kinase Inhibitor 1B,Cyclin Dependent Kinase Inhibitor p27,Kip1 Protein, p27,p27, CDK Inhibitor

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