Study of Aging Effect on the Progression of Restenosis: Establishment of the Platform for Screening the Drugs Targets with Suppressing Effect on Platelet-Derived Growth Factor Receptor-Beta

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Aging society seems to be a problem for many nations. Our preliminary data implicated that aging reduced the incidence rate and severity of restenosis based on the animal model and clinical statistics with small sample size. Besides, the expression and activity levels of PDGF receptor-β (PDGFRB) were downregulated dramatically in the experimental studies of cell senescence. Accordingly, the purposes of this project are to clarify the correlation and mechanisms between age and restenosis. This project will be divided into three research focuses: Research focus 1: Different cell senescence models will be used to clarify the regulatory effects and mechanisms of cell senescence or aging in the transcription, translational and post-translational levels of PDGFRB. Besides, the promoter-binding transcription factor profile assay and luciferase-based promoter assay system will be used to evaluate the roles and significance of candidate transcription factors on regulation of PDGFRB. These candidate transcription factors would be the screening targets and to combine with luciferase-based promoter assay system to co-construct the drug screening platform used in screening the bioactive compound with suppressive effect on PDGFRB expression. Furthermore, application values of these candidate transcription factors for used as novel drug targets will be evaluated by siRNA technology in animal model of restenosis. Research focus 2: To investigate the effect of ageing on restenosis by using restenosis model of SMAP8 mice. In adiition, the mechanism difference between aging and cell senescence on PDGFRB regulation will be evaluated by using pathological sections and primary VSMCs studies. The level change of serum PDGF-BB will also be included as experimental factor to clarify aging effects on restenosis. Research focus 3: To analyze the difference and correlation of the incidence rate of restenosis between the younger and elder patients with stent implantation by using clinical retrospective study for evaluating whether age is a possible reference for the clinical choice of vascular stents (bare-metal stent or drug-eluting stent).
StatusFinished
Effective start/end date8/1/167/31/17