Pathomechanistic role of Igf2bp2 during cardiac stress: induction of remodeling and cardiac hypertrophy

The Igf2bp proteins are a family of RNA binding proteins, consisting of 3 paralogs that are highly conserved in vertebrates and help regulate RNA localization, stability, translation, and alternative splicing in various systems. Although Igf2bp1 and Igf2bp3 are considered to be oncofetal proteins, Igf2bp2 continues to be expressed in many tissues and cell types after birth as well as throughout embryonic development. We have discovered a novel role for Igf2bp2 in the remodeling of the heart that takes place after cardiac ischemia, such as occurs during myocardial infarction. Analysis of available data from a number of studies indicates that both ischemic and non-ischemic stresses lead to upregulation of Igf2bp2 in the heart. Conversely, during recovery of stressed, dilated cardiac hypertrophy (DCH), hearts- Igf2bp2 levels are downregulated. We have found that overexpression of Igf2bp2 from embryogenesis onward, causes the mice to develop DCH and die 2-3 weeks after birth. When Igf2bp2 expression is turned off following birth, however, the mice develop normally. Induction of Igf2bp2 expression at 5-6 weeks of age caused DCH, impaired function and death. We are using both primary cardiomyocytes and genetic mouse models to identify potential targets of Igf2bp2 and understand its mechanism of action.