MZF1 is differentially expressed in human cardiac tissue of different age and c-KIT⁺ progenitor cells in the human adult heart

Objectives: The paradigm of a quiescent myocardium is obsolete since several resident progenitor cell populations have been identified within the heart by well-known stem cell surface markers like Sca1 or c-Kit. Recently we identified a potential role of the transcription factor myeloid zinc finger 1 (Mzf1) during murine embryonic heart development. Therefore, we investigated the role of MZF1 in human cardiac tissue of various age and in resident c-KIT⁺ progenitor cells obtained from the human adult heart.

Methods: Human tissue was derived from atrial or ventricular biopsies of patients (aged from 4 month to 75 years) undergoing heart surgery at the German Heart Center Munich. For gene expression analysis by qRT-PCR biopsies were directly snap-frozen in liquid nitrogen after the surgical procedure. For magnetic activated cell sorting (MACS) heart biopsies from adults were put into physiological Ringer's Solution. Single cell suspension was prepared and MACS was performed with an anti-c-KIT antibody. Gene expression within the c-KIT⁺ and the c-KIT⁻ cell population was compared by qRT-PCR.

Results: MZF1 expression was increased about 160-fold in cardiac tissue samples from infants ( < 7 months) compared to aged adults (> 65 years). An average amount of 3.1% ± 1.1% c-KIT⁺ cells could be isolated from human adult heart tissue by MACS. An 18-fold elevated c-KIT expression was confirmed by qRT-PCR in the c-KIT⁺ over the c-KIT⁻ cells (p = 0.002). MZF1 was increased about 3-fold in the c-KIT⁺ resident progenitor cells compared to their c-KIT⁻ counterparts (p = 0.035).

Conclusion: It could be shown that MZF1 expression levels were increased in infantile compared to aged cardiac tissue which is in line with previous results obtained from a mouse model. Furthermore MZF1 was differentially expressed in a human c-KIT⁺ cardiac progenitor cell population, which showed a significant improvement of cardiac function and a reduction of infarct size in the recently published SCIPIO trial. These facts may indicate a role of MZF1 in the infantile human heart and in resident c-KIT⁺ cardiac progenitor cells.