HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Knockdown of microRNA-181 by lentivirus mediated siRNA expression vector decreases the arrhythmogenic effect of skeletal myoblast transplantation in rat with myocardial infarction.

Abstract
The arrhythmogenic effect of intracardiac skeletal myoblast (SKM) transplantation may be related to the differentiation state of SKMs. We tested the hypothesis that lentivirus mediated siRNA against the loop region of miRNA-181a could upregulate the SKMs differentiation repressor homeobox protein A11 (Hox-A11) and reduce the arrhythmias post SKM transplantation into ischemic myocardium of rats. Primary cultured SKMs were transfected with Lenti-siR-miR-181 (recombined lentivirus expressing the unique siRNA against miR-181a, LV group). Real-time PCR showed that miRNA-181a level was significantly decreased and Hox-A11 protein level significantly increased in LV group than in control group at days 5 and days 7 post Lentivirus transfection. Knockdown of miRNA-181a significantly promoted SKMs' growth and attenuated the connexin43 downregulation in SKMs in vitro. Seven days after left coronary artery ligation, rats were randomized to receive intramyocardial injection of either 5x10(6) SKMs transfected with Lenti-siR-miR-181 (MI-SKMLV), 5x10(6) Lenti-siLUC SKMs (MI-SKM) or PBS (MI-PBS). Systolic function was significantly improved in both MI-SKM and MI-SKMLV groups fourteen days after injection. Incidence of inducible self-terminating ventricular tachycardia was significantly lower in MI-SKMLV than that in MI-SKM group. Engraftments of SKMs with knockdowned miRNA-181a similarly improved cardiac function as SKM transplantation but significantly decreased the arrhythmogenic effect of SKM transplantation in rats with experimental myocardial infarction.
AuthorsYi-Gang Li, Peng-Pai Zhang, Kun-Li Jiao, Yun-Zeng Zou
JournalMicrovascular research (Microvasc Res) Vol. 78 Issue 3 Pg. 393-404 (Dec 2009) ISSN: 1095-9319 [Electronic] United States
PMID19595696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Homeodomain Proteins
  • MicroRNAs
  • RNA, Small Interfering
Topics
  • Animals
  • Cell Transplantation (adverse effects)
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Gene Silencing
  • Homeodomain Proteins (genetics, metabolism)
  • MicroRNAs (genetics, metabolism)
  • Myoblasts, Skeletal (metabolism, transplantation)
  • Myocardial Infarction (genetics, physiopathology, therapy)
  • RNA, Small Interfering (genetics)
  • Rats
  • Rats, Sprague-Dawley
  • Tachycardia, Ventricular (etiology, genetics, therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: