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Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model

Title
Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model
Authors
Hahn W.Pyun W.-B.Kim D.-S.Yoo W.-S.Lee S.-D.Won J.-H.Shin G.J.Kim J.-M.Kim S.
Ewha Authors
신길자편욱범
SCOPUS Author ID
신길자scopus; 편욱범scopus
Issue Date
2011
Journal Title
Journal of Gene Medicine
ISSN
1099-498XJCR Link
Citation
vol. 13, no. 10, pp. 549 - 555
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background: The therapeutic potential of pCK-HGF-X7, a naked DNA designed to express two isoforms of hepatocyte growth factor (HGF 723 and HGF 728), was studied in the rat ischemic heart disease model. Methods: First, the kinetics of gene expression was examined by injecting pCK-HGF-X7 DNA into the rat heart. Second, the cardioprotective effects were compared between the two naked DNA constructs, expressing a single (HGF 728) or both isoforms (HGF 728 and HGF 723) of HGF, in the rat ischemic heart disease model. The ischemic injury to the rat heart was created by ischemia-reperfusion in the anterior descending artery. The respective naked DNA constructs were injected into the anterior wall of the rat heart with the ischemia-reperfusion injury. Cardiac function, capillary density and anti-fibrotic activity were compared between the two naked DNA constructs. Results: The intramyocardial administration of pCK-HGF-X7 resulted in transient and localized HGF expression for 3weeks. At its peak, approximately 678pg (per mg of tissue protein) of HGF was produced in the injected heart without an increase of HGF protein level in other tissues, and serum. pCK-HGF-X7 more efficiently improved the left ventricular ejection fraction and the systolic anterior wall thickness, increased the capillary density, and inhibited myocardial fibrosis, in a statistically significant manner, compared to the identical vector encoding HGF 728 only. Conclusions: These results demonstrate that transfer of the genomic-cDNA hybrid expressing both isoforms of the HGF gene might provide higher therapeutic effects than the cDNA sequence producing HGF 728 alone in the treatment of ischemic heart disease. © 2011 John Wiley & Sons, Ltd.
DOI
10.1002/jgm.1603
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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