Direct injection of Kit ligand-2 lentivirus improves cardiac repair and rescues mice post-myocardial infarction

Koji Higuchi, Bilal Ayach, Takeya Sato, Manyin Chen, Sean P. Devine, Vanessa I. Rasaiah, Fayez Dawood, Teruyuki Yanagisawa, Chuwa Tei, Toshihiro Takenaka, Peter P. Liu, Jeffrey A. Medin

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Myocardial infarction (MI) and subsequent adverse remodeling cause heart failure. Previously we demonstrated a role for Kit ligand (KL) in improving cardiac function post-MI. KL has two major isoforms; KL-1 is secreted whereas KL-2 is predominantly membrane bound. We demonstrate here first that KL-2-deficient mice have worse survival and an increased heart/bodyweight ratio post-MI compared to mice with reduced c-Kit receptor expression. Next we synthesized recombinant lentiviral vectors (LVs) that engineered functional expression of murine KL-1 and KL-2. For in vivo analyses, we directly injected these LVs into the left ventricle of membrane-bound KL-deficient Sl/Sld or wild-type (WT) mice undergoing MI. Control LV/enGFP injection led to measurable reporter gene expression in hearts. Injection of LV/KL-2 attenuated adverse left ventricular remodeling and dramatically improved survival post-MI in both Sl/Sld and WT mice (from 12 to 71% and 35 to 73%, respectively, versus controls). With regard toward beginning to understand the possible salutary mechanisms involved in this effect, differential staining patterns of Sca-1 and Ly49 on peripheral blood (PB) cells from therapeutically treated animals was found. Our data show that LV/KL-2 gene therapy is a promising treatment for MI.

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalMolecular Therapy
Volume17
Issue number2
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Direct injection of Kit ligand-2 lentivirus improves cardiac repair and rescues mice post-myocardial infarction'. Together they form a unique fingerprint.

Cite this