Direct injection of kit ligand-2 lentivirus improves cardiac repair and rescues mice post-myocardial infarction. Mol Ther 2009 Feb;17(2):262-8
Date
11/13/2008Pubmed ID
19002160Pubmed Central ID
PMC2835055DOI
10.1038/mt.2008.244Scopus ID
2-s2.0-63649139251 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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/Sl(d) 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/Sl(d) 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.
Author List
Higuchi K, Ayach B, Sato T, Chen M, Devine SP, Rasaiah VI, Dawood F, Yanagisawa T, Tei C, Takenaka T, Liu PP, Medin JAAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Genetic Vectors
Green Fluorescent Proteins
Immunohistochemistry
Injections
Lentivirus
Mice
Myocardial Infarction
Myocardium
Stem Cell Factor
