Abstract 14685: Re Expression of Isl-1, a Transcription Factor Mastering Embryonic Cardiogenesis, in Acute Myocardial Infarction Patients
Background - The transcription factor Isl1 plays a crucial role in the embryonic development of the heart and its vasculature, and gives rise to hematopoietic progenitors in the spleen and bone marrow. Isl1 expression is maintained in adult cardiac and splenocyte progenitors, and its expression promotes differentiation to the cardiac lineages and angiogenesis. It is yet unknown whether Isl1 stem cells are mobilized to peripheral blood and whether or not they contribute to regeneration in ischemic heart disease (IHD).
Objective- To examine whether circulating human stem cells express Isl1; and to assess Isl1's expression patterns in patients suffering from IHD or from its risk factors.
Methods - 72 patients admitted to the Cath Lab and diagnosed with acute myocardial infarction (AMI) or with normal coronaries were enrolled. In order to verify Isl1 expression, mononuclear cells were extracted from whole blood. The number of stem cells expressing Isl1, and the phenotypic characterization of the cells was studied by FACS analysis and by RT-PCR. Isl1 expression level in AMI patients was compared to its level in patients with normal coronaries. In order to determine the influence of IHD risk factors on Isl1 expression, Isl1 levels were correlated to IHD risk factors in the normal coronaries group.
Results - Isl1 is expressed in circulating human hematopoietic stem cells (3.16%±0.5, n=72). Isl1 expression was markedly higher in patients experiencing AMI in comparison to patients with normal coronaries. Reduced Isl1 expression correlated with Diabetes Mellitus type 2 (DMII) (1.35±1.12 vs. 4.04±3 p=0.01); a similar trend was seen in smokers. Increased Isl1 expression correlated with hypertension (4.29±3.3 vs. 1.28±1.9 p=o.o1); a similar trend was seen in patients with high CRP levels.
Conclusion - These data are the first evidence of up regulation and mobilization of Isl1+ stem cells in cases exhibiting a need for angiogenesis and vascular repair (e.g. hypertension and AMI), as opposed to their reduced activity in processes showing decreased angiogenic capacity (e.g. DMII and smoking). These Results suggest that Isl1 has an active role in endogenous regenerative attempts. The Isl1 gene appears to be an attractive target for future cardiac gene therapy in IHD patients.
- © 2012 by American Heart Association, Inc.