title: Endothelial cells regulate cardiac myocyte reorganisation through β1-integrin signalling.
abstract: BACKGROUND
  In normal hearts, capillaries are densely distributed throughout the myocardial tissue, and the cross-talk between myocytes and capillary endothelial cells plays a pivotal role in regulating cardiac development, maturation and function. Although previous studies have suggested a role for the endothelium in the organisation of nearby cardiomyocytes, the underlying mechanism has yet to be illustrated.
  
  
  RESULTS
  Using a transwell coculture system, we studied the paracrine effect of endothelial cells on cardiomyocytes and found that the regulation of cardiomyocyte spatial reorganisation and cytoskeletal dynamics by endothelial cells was coupled with β1-integrin induction. To determine the role of β1-integrin in this process, we preincubated myocytes with a β1-integrin function-blocking antibody before coculture. β1-integrin blockage abolished myocyte chemotactic activity and inhibited microtubule extension and stress fibre assembly. We further evaluated the therapeutic potential of combined endothelial cell-cardiac myocyte transplantation against ischemic cardiomyopathy in an acute myocardial infarction (AMI) mouse model. The results showed that myocytes and endothelial cells synergistically promoted ischemic myocardial repair, as evidenced by the robust engraftment and migration of implanted cells within the infarcted area, as well as the stimulation of angiogenesis, the attenuation of scar tissue and the improvement of cardiac function.
  
  
  CONCLUSIONS
  Our study demonstrated the necessity of β1-integrin in the interactions between cardiomyocytes and endothelial cells and presented a novel combined transplantation approach that might hold promise for treating ischemic cardiomyopathy.
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.forename: Renyue
authors.initials: R
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Lian
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D012038:Regeneration; D015398:Signal Transduction; D014184:Transplantation, Homologous; D014463:Ultrasonography
chemical_list: D019012:Integrin beta1