Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model

نویسندگان

  • Christian Klopsch
  • Dario Furlani
  • Ralf Gäbel
  • Wenzhong Li
  • Erik Pittermann
  • Murat Ugurlucan
  • Guenther Kundt
  • Christiana Zingler
  • Ulf Titze
  • Weiwei Wang
  • Lee-Lee Ong
  • Klaus Wagner
  • Ren-Ke Li
  • Nan Ma
  • Gustav Steinhoff
چکیده

Erythropoietin (EPO) protects the myocardium from ischaemic injury and promotes beneficial remodelling. We assessed the therapeutic efficacy of intracardiac EPO injection and EPO-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, EPO (3000 U/kg) or saline was delivered by intracardiac injection. Compared to myocardial infarction control group (MIC), EPO significantly improved left ventricular function (n =11-14, P < 0.05) and decreased right ventricular wall stress (n = 8, P < 0.05) assessed by pressure-volume loops after 6 weeks. MI-EPO hearts exhibited smaller infarction size (20.1 +/- 1.1% versus 27.8 +/- 1.2%; n = 6-8, P < 0.001) and greater capillary density (338.5 +/- 14.7 versus 259.8 +/- 9.2 vessels per mm2; n = 6-8, P < 0.001) than MIC hearts. Direct EPO injection reduced post-MI myocardial apoptosis by approximately 41% (0.27 +/- 0.03% versus 0.42 +/- 0.03%; n = 6, P= 0.005). The chemoattractant SDF-1 was up-regulated significantly assessed by quantitative realtime PCR and immunohistology. c-Kit(+) and CD34(+) stem cells were significantly more numerous in MI-EPO than in MIC at 24 hrs in peripheral blood (n = 7, P < 0.05) and 48 hrs in the infarcted hearts (n = 6, P < 0.001). Further, the mRNAs of Akt, eNOS and EPO receptor were significantly enhanced in MI-EPO hearts (n = 7, P < 0.05). Intracardiac EPO injection restores myocardial functions following MI, which may attribute to the improved early recruitment of c-Kit(+) and CD34(+) stem cells via the enhanced expression of chemoattractant SDF-1.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model

Matrigel promotes angiogenesis in the myocardium from ischemic injury and prevents remodelling of the left ventricle. We assessed the therapeutic efficacy of intracardiac matrigel injection and matrigel-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, matrigel (250 μl) or phosphate-buffered solution (PBS) was delivered by intracardiac injection. Compared to the...

متن کامل

Transplantation of Cardiogenic Pre-Differentiated Autologous Adipose-Derived Mesenchymal Stem Cells Induced by Mechanical Loading Improves Cardiac Function Following Acute Myocardial Infarction in Rabbit Model

Objective- Investigate myocardial performance after autologous adipose-derived (ASCs) mesenchymal stem cell differentiated under equiaxial cyclic strain, transplantation in rabbits with acute myocardial infarction (AMI). Design- Prospective, randomized experimental study Animals- 20 New Zealand White rabbits (2-3 kg) P...

متن کامل

The Effect of Eight Weeks of Intermittent Training with Quercetin Encapsulated Nanoparticles on JNK and ERK Apoptosis Regulators in the Rat Model of Myocardial Infarction

Introduction: Restoration of blood flow to the ischemic heart muscle causes infarction and myocyte death. Quercetin can be effective in treating heart disease due to its antioxidant effect, but its use is limited due to its low solubility in water. Quercetin restriction can be removed by embedding it in carrier nanoparticles. The present study was designed to determine the effect of quercetin e...

متن کامل

Translation of Methdology used in Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction

Background: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly used rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to int...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 13  شماره 

صفحات  -

تاریخ انتشار 2009