Biomaterial Database

Deficiency of clusterin inhibits neointimal hyperplasia after vascular injury. 2009

Takahiro Shirasawa, and Masaaki Miyata, and Hideyuki Eto, and Narisato Hamada, and Yuichi Akasaki, and Takahiro Miyauchi, and Yuko Furusho, and Koji Orihara, and Shuichi Hamasaki, and Bruce J Aronow, and Jonathan D Smith, and Chuwa Tei

Department of Cardiovascular, Respiratory and Metabolic Medicine, Kagoshima University, Japan.

OBJECTIVE Increased clusterin mRNA and protein levels have been detected in various tissues undergoing stress, and we previously reported that clusterin is markedly induced in media and neointima following vascular injury. The present study therefore investigated the impact of clusterin on neointimal hyperplasia following vascular injury. RESULTS As compared with wild-type mice, clusterin knockout mice (clusterin-KO) demonstrated a significant decrease of the intima/media ratio 4 weeks after cuff placement. Immunohistochemical analysis of injured femoral arteries in clusterin-KO demonstrated the accumulation of p53 in nuclei of neointimal vascular smooth muscle cells (VSMCs). Moreover, VSMCs from either clusterin-KO or rat VSMCs treated with clusterin-short-interfering (si) RNA subjected to static stretch exhibited significantly increased p53 and p21, and increased G1 cell cycle arrest as indicated by flow cytometry compared with VSMCs from wild-type mice. CONCLUSIONS Reduced clusterin expression reduced the proliferation of VSMCs and induced G1 arrest via p53 and p21. Clusterin therefore represents a promising molecular target to limit restenosis after coronary intervention.

UI	MeSH Term	Description	Entries
D006965	Hyperplasia	An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.	Hyperplasias
D008297	Male		Males
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
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
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
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D016193	G1 Phase	The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.	First Gap Phase,G1a Phase,G1b Phase,Gap Phase 1,First Gap Phases,G1 Phases,G1a Phases,G1b Phases,Gap Phase, First,Gap Phases, First,Phase 1, Gap,Phase, First Gap,Phase, G1,Phase, G1a,Phase, G1b,Phases, First Gap,Phases, G1,Phases, G1a,Phases, G1b
D017539	Tunica Intima	The innermost layer of an artery or vein, made up of one layer of endothelial cells and supported by an internal elastic lamina.	Internal Elastic Lamella,Internal Elastic Lamina,Tunica Intima Vasorum,Vascular Intima,Arterial Intima,Venous Intima,Arterial Intimas,Elastic Lamella, Internal,Elastic Lamina, Internal,Internal Elastic Laminas,Intima, Arterial,Intima, Vascular,Intima, Venous,Lamella, Internal Elastic,Lamina, Internal Elastic,Vascular Intimas,Venous Intimas
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
D051152	Clusterin	A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.	ApoJ Protein,Apolipoprotein J,Complement Lysis Inhibitor,Complement-Associated Protein SP-40,40,Ionizing Radiation-Induced Protein-8,MAC393 Antigen,SGP-2 Protein,SP 40,40 Protein,Sulfated Glycoprotein 2,Sulfated Glycoprotein-2,TRPM-2 Protein,Testosterone-Repressed Prostate Message-2 Protein,X-Ray-Inducible Protein 8,XIP8 Protein,Complement Associated Protein SP 40,40,Ionizing Radiation Induced Protein 8,Radiation-Induced Protein-8, Ionizing,SGP 2 Protein,SP-40,40, Complement-Associated Protein,TRPM 2 Protein,Testosterone Repressed Prostate Message 2 Protein,X Ray Inducible Protein 8