• DOI:10.1093/cvr/cvp386
• Corpus ID: 10544349

Midkine gene transfer after myocardial infarction in rats prevents remodelling and ameliorates cardiac dysfunction.

@article{Sumida2010MidkineGT,
  title={Midkine gene transfer after myocardial infarction in rats prevents remodelling and ameliorates cardiac dysfunction.},
  author={Arihiro Sumida and Mitsuru Horiba and Hisaaki Ishiguro and Hiroharu Takenaka and Norihiro Ueda and Hiroaki Ooboshi and Tobias Opthof and Kenji Kadomatsu and Itsuo Kodama},
  journal={Cardiovascular research},
  year={2010},
  volume={86 1},
  pages={
          113-21
        }
}

• A. Sumida, M. Horiba, +6 authors I. Kodama
• Published 1 April 2010
• Biology, Medicine
• Cardiovascular research

AIM
We have previously reported that therapy with midkine (MK) has a protective effect in mouse models of myocardial infarction (MI) and ischemia/reperfusion. The underlying mechanism was proved to be anti-apoptosis and prevention of left ventricular (LV) remodelling following angiogenesis. Here we investigated the effects of overexpression of MK by adenoviral gene transfer on cardiac function and remodelling in an experimental rat MI model.

METHODS AND RESULTS
MI was created in male Wistar rats. Adenoviral vectors encoding mouse MK (AdMK) or beta-galactosidase (AdLacZ; as controls) were injected in myocardium at the onset of MI. One week after injection, in vivo adenoviral gene expression was assessed by western blot and histological analysis. After echocardiographic analysis at 4 weeks and haemodynamic analysis at 6 weeks after MI, AdMK animals had better cardiac function compared with AdLacZ animals. Heart weight (HW) and relative HW of AdMK animals were not different from sham-operated animals after 6 weeks, pointing to a very potent effect in the prevention of ischemic cardiomyopathy. In histological studies at 6 weeks after MI, AdMK animals had less fibrosis in the non-infarcted myocardium and higher vascular density in the border-zone area compared with AdLacZ animals. AdMK animals had strongly upregulated levels of phosphorylated extracellular signal-regulated kinase, Akt, PI 3-kinase, and Bcl-2, whereas the level of Bax was downregulated compared with AdLacZ animals.

CONCLUSION
Overexpression of MK prevents LV remodelling and ameliorates LV dysfunction by anti-apoptotic and pro-angiogenic effects. MK gene transfer may provide a new therapeutic modality in ischemic cardiomyopathy and ischemic heart failure.