Genonic analysis to Identify atherosclerosis-susceptible and -resistant genes and Investigation of molecular mechanism In the pathogenesis of atherosclerosis

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyushu University
• Principal Investigator: KOIKE George Kyushu University Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Assistant Professor, 大学病院, 助手 (90325522)
• Co-Investigator(Kenkyū-buntansha): ICHIKI Toshihiro Kyushu University Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Assistant Professor, 大学病院, 助手 (80311843) ; EGASHIRA Kensuke Kyushu University Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Associate Professor, 大学病院, 講師 (60260379)
• Project Period (FY): 2002 – 2003
• Keywords: Atherosclerosis / ischemic heart disease / Expression Profiling / Polymorphisms / Genetic analysis / Animal model

Research Abstract

Specific aims of this project are (1)to Identify atherosclerosis-susceptible and -resistant genes by analyzing atherosclerosis-susceptible and -resistant mice, and (2)to carry out genetic analysis by using single nucleotide polymorphisms (SNPs) of candidate genes and newly identified atherosclerosis-susceptible and -resistant genes. Progress of this project is as follows;
1. Identification of atherosclerosis-susceptible and -resistant genes
To identity atherosclerosis-susceptible and -resistant genes, atherosclerosis-susceptible mouse line (C57BL/6J) and atherosclerosis -resistant mouse line (C3H/HeJ), were fed with high cholesterol diet. Subsequently, mRNAs were extracted from vascular endothelial cells, vascular smooth muscle cells and bone marrow stem cells of these animals for expression profiling (In viva expression profiling) with cDNA microarray chips. Expression profiling was carried out, and collected data are now under analysis. At the same time, optimization for generating pri mary cultured cells from vascular endothelial cells, vascular smooth muscle cells and bone marrow stem cells of these animals are undergone to perform in vitro expression profiling.
2.Identification of sequence variations in atherosclerosis-related candidate genes for genetic analysis
Among several candidate genes experimental condition to determine MCP-1 A-2518G polymorphism and CCR2 G270A polymorphism has been set. Then, polymorphisms of candidate genes, such as MCP-1,TGF-β and NF-κB, were searchd, but no novel polymorphisms to alter gene function were identified. At the same time, recruitment of ischemic heart diseasee(IHD)patients has been continued,but only 2 out of 300 IHD patients were found. Our patient database was reanalyzed, and It was identified that number of coronary risk factors had an small influence on the pathogenesis of atherosclerosis. Therefore, a strategy of patient recruitment was changed, and recruitment of IHD patients with new criteria was begun. ln future, genetic analysis using polymorphisms of aterosclerosis-related candidate genes will be conducted.