Endothelial progenitor cell mediates transport of hepatitis B virus into myocardial tissue  

作　　者：RONG Qi-fei HUANG Jun SU En-ben LI Jun LI Jian-yong ZHANG Li-li CHEN Lei-lei WANG Xiao-bin CAO Ke-jiang 

机构地区：[1]Department of Cardiology , First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [2]Department of Infectious Disease , First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [3]Department of Hematology , First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

出　　处：《Chinese Medical Journal》2008年第3期248-256,共9页中华医学杂志（英文版）

基　　金：This work was supported in part by a grant from the National Natural Science Foundation of China （No. 30370575）.Acknowledgments： We are grateful to Dr. FENG Jian-hua for his useful suggestions and preparing the manuscript and to Prof. WANG Yang （Institute of Biochemistry, Shanghai, China） for providing HBV genomic clone pHBV.

摘　　要：Background Hepatitis B virus （HBV） replication has been reported to be involved in many extrahepatic viral disorders; however, the mechanism by which HBV is transinfected into extrahepatic tissues such as myocardium and causes HBV associated myocarditis remains largely unknown. Methods In this study, endothelial progenitor cells （EPCs） were infected by HBV and then transfused into ischemic model of mice. HBV surface and core antigen as well as mutation of HBV particles were detected by immunohistochemistry, fluorescent activated cell sorter and transmission electron microscopy in vitro and in vivo. Results Human cord blood EPCs, but not human umbilical vein endothelial cells （HUVECs） could be effectively infected by taking up HBV in vitro. HBV envelope surface and core antigen expressions were first detectable in EPCs at day 3 after virus challenge, sustained for up to 11 days, and decreased thereafter. Similarly, the virus particles were the most abundant in EPCs in the first week observed by a transmission electron microscope, and declined in 3 weeks after HBV infection. HBV DNA but not HBV cccDNA in EPCs were detectable even 3 weeks after virus challenge, as shown by PCR analysis. Furthermore, intravenous transplantation of HBV-treatod EPCs into myocardial infarction Sprague ＆ Dawley rats model resulted in incorporation of both EPCs and HBV into injured endothelial tissues of capillaries in the ischemic border zone. Conclusions These results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured myocardial tissues. The findings might suggest a novel mechanism for HBV-associated myocarditis.Background Hepatitis B virus （HBV） replication has been reported to be involved in many extrahepatic viral disorders; however, the mechanism by which HBV is transinfected into extrahepatic tissues such as myocardium and causes HBV associated myocarditis remains largely unknown. Methods In this study, endothelial progenitor cells （EPCs） were infected by HBV and then transfused into ischemic model of mice. HBV surface and core antigen as well as mutation of HBV particles were detected by immunohistochemistry, fluorescent activated cell sorter and transmission electron microscopy in vitro and in vivo. Results Human cord blood EPCs, but not human umbilical vein endothelial cells （HUVECs） could be effectively infected by taking up HBV in vitro. HBV envelope surface and core antigen expressions were first detectable in EPCs at day 3 after virus challenge, sustained for up to 11 days, and decreased thereafter. Similarly, the virus particles were the most abundant in EPCs in the first week observed by a transmission electron microscope, and declined in 3 weeks after HBV infection. HBV DNA but not HBV cccDNA in EPCs were detectable even 3 weeks after virus challenge, as shown by PCR analysis. Furthermore, intravenous transplantation of HBV-treatod EPCs into myocardial infarction Sprague ＆ Dawley rats model resulted in incorporation of both EPCs and HBV into injured endothelial tissues of capillaries in the ischemic border zone. Conclusions These results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured myocardial tissues. The findings might suggest a novel mechanism for HBV-associated myocarditis.

关 键 词：MYOCARDITIS INFECTION myocardial infarction cord blood ANGIOGENESIS 

分 类 号：R542.22[医药卫生—心血管疾病]