Islet-1 gene delivery improves myocardial performance after experimental infarction

Aya Barzelay, Edith Hochhauser, Michal Entin-Meer, Yelena Chepurko, Einat Birk, Arnon Afek, Iris Barshack, Lidya Pinhas, Yulia Rivo, Jeremy Ben-Shoshan, Sofia Maysel-Auslender, Gad Keren, Jacob George*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The LIM-homeobox transcription factor Isl1 plays a crucial role during heart embryogenesis and later on gives rise to adult resident cardiac stem cells. In this study, we aimed to discover new extra cardiac populations of Isl1 stem cells. We then investigated endogenous Isl1 kinetics after myocardial infarction (MI), and the effect of intra-myocardial gene transfer of naked DNA encoding Isl1 on functional recovery after MI. Methods: We used the transgenic mice Isl1/cre/Z/EG for lineage tracing of extra cardiac Isl1 stem cells. Non transgenic mice were used to study Isl1 kinetics post-MI by RT-PCR and FACS analysis. MI was induced in non transgenic mice by permanent ligation of the left anterior descending coronary artery (LAD). Naked DNA encoding Isl1 was injected to the peri-infarct region. Evaluation of cardiac performance was conducted by echocardiogram. Analysis of myocardial fibrosis and number of vessels was performed on histological cryosections. Results and conclusions: Isl1 gives rise to subpopulations of progenitors in both the bone marrow and spleen, and is re-expressed in the spleen and left ventricle following MI. Intramyocardial gene transfer of Isl1 to the border zone of the infarcted hearts resulted in partial salvage of left ventricular function, enhanced vascularization, and reduced myocardial fibrosis.The Isl1 gene appears to be an attractive reparative target for future management of myocardial dysfunction.

Original languageEnglish
Pages (from-to)284-290
Number of pages7
JournalAtherosclerosis
Volume223
Issue number2
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Angiogenesis
  • Gene therapy
  • Myocardial infarction

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