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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-3-10
pubmed:abstractText
The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) promotes vascular smooth muscle (VSMC) proliferation. However, the signaling pathways mediating CAMKII-dependent proliferative effects in vivo are poorly understood. This study tested the hypothesis that CaMKII? mediates neointimal proliferation after carotid artery ligation by regulating expression and activity of cell cycle regulators, particularly at the G1/S checkpoint. Data herein indicate that 14 days after carotid ligation, C57Bl/6 mice developed a marked neointima with robust CaMKII protein expression. In particular, only the CaMKII isoform ? was increased as demonstrated by quantitative RT-PCR. Genetic deletion of CaMKII ? prevented injury-induced neointimal hyperplasia and cell proliferation in the intima and media. In ligated carotids of control mice, the proliferative cell cycle markers cdk2, cyclin E, and cyclin D1 were activated. In contrast, in CaMKII?(-/-) mice, we detected a reduction in proliferative cell cycle regulators as well as an increase in the cell cycle inhibitor p21. This expression profile was confirmed in cultured CaMKII?(-/-) VSMC, in which cdk2 and cdk4 activity was decreased. Toward understanding how CAMKII? affects p53, a transcriptional regulator of p21, we examined p53 pathway components. Our data indicate that p53 is elevated in CAMKII?(-/-) VSMC, whereas phosphorylation of the p53-specific E3 ligase, Mdm2, was decreased. In conclusion, CaMKII stimulates neointima proliferation after vascular injury by regulating cell proliferation through inhibition of p21 and induction of Mdm-2-mediated degradation of p53.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Mdm2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7990-9
pubmed:dateRevised
2011-10-14
pubmed:meshHeading
pubmed-meshheading:21193397-Animals, pubmed-meshheading:21193397-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:21193397-Carotid Arteries, pubmed-meshheading:21193397-Cyclin-Dependent Kinase 2, pubmed-meshheading:21193397-Cyclin-Dependent Kinase 4, pubmed-meshheading:21193397-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:21193397-G1 Phase, pubmed-meshheading:21193397-Gene Expression Regulation, Enzymologic, pubmed-meshheading:21193397-Mice, pubmed-meshheading:21193397-Mice, Knockout, pubmed-meshheading:21193397-Myocytes, Smooth Muscle, pubmed-meshheading:21193397-Neointima, pubmed-meshheading:21193397-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:21193397-S Phase, pubmed-meshheading:21193397-Tumor Suppressor Protein p53, pubmed-meshheading:21193397-Ubiquitin-Protein Ligases
pubmed:year
2011
pubmed:articleTitle
The multifunctional Ca2+/calmodulin-dependent kinase II delta (CaMKIIdelta) controls neointima formation after carotid ligation and vascular smooth muscle cell proliferation through cell cycle regulation by p21.
pubmed:affiliation
Division of Cardiovascular Medicine/Department of Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural