接头分子Cbl与血管再狭窄的防治课件

1、Fighting Restenosis: Targeting c-CblNanping WangInstitute of Cardiovascular SciencePeking University1Coronary artery disease: a significant health threat afflicting millions of individuals worldwide. Despite the development of a variety of technologies and catheter based interventions, post-procedur

2、e restenosis is still a significant concern. Gene therapy has emerged as a promising approach aimed at modifying cellular processes that give rise to restenosis. Restenosis2Gene Therapy-Preclinical Study Rissanen and Yla-Herttuala. Mol Ther. 2007;15:1233-473c-CblCellular homologue of retroviral onco

3、genic protein v-Cbl which induces Casitas B-lineage lymphoma. An adaptor protein and an E3 ubiquitin ligase. Tyrosine phosphorylated in response to various including integrins and activation of receptor tyrosine kinases (PDGFR and FGFR). 4Aim of the StudyTo determine the pathophysiological role of c

4、-Cbl in vascular injury response in SMCs in vitro and balloon-injured arteries in vivo.5c-Cbl Tyrosine Phosphorylation Is Increased in Injured Arteries6PDGF Increased c-Cbl Tyrosine Phosphorylation in SMCs7Conditional Expression of c-Cbl Mutant in SMCs10c-Cbl-m Suppressed SMC Proliferation and Migra

5、tion 11c-Cbl-m Restricted G1/S Progression in SMCs12c-Cbl-m Increased Ubiquitination of PDGF and FGF Receptors 16Adenovirus-mediated Gene Transfer of c-Cbl-m Inhibits Akt/mTOR Activation in vivo17c-Cbl-m Inhibits SMC Proliferation and Migration in vivo18c-Cbl-m Inhibits Intimal Hyperplasia in Balloon-injured Arteries19AcknowledgmentNational Science Foundation