Stress-induced cardiomyopathy linked to IGF2BP2 RNA binding protein

Hebrew University, Hadassah Medical Center, and Martin-Luther University Halle-Wittenburg researchers Discover the Importance of IGF2BP2 in Cardiac Stress Response. The study reveals the function of IGF2BP2, an RNA binding protein, in responding to cardiac stress. It demonstrates how increased IGF2BP2 expression causes dilated cardiomyopathy (DCM) and eventual mortality, but that a controlled reduction in expression results in recovery, implying that it may be reversible. The study also links elevated IGF2BP2 levels to DCM or myocardial infarction, implying therapeutic importance. These findings provide a new understanding of stress-induced cardiomyopathy and pave the way for novel therapeutic techniques, establishing IGF2BP2 as a prospective target for treating a variety of cardiac disorders and potentially revolutionizing patient care in this arena.

A new study has revealed information about the role of the RNA binding protein IGF2BP2 in stress-induced cardiac problems.

Researchers have long been intrigued by the IGF2BP family of RNA binding proteins, which are renowned for their regulatory influence on intracellular RNA dynamics. While IGF2BP1 and 3 have been linked to oncofetal features, IGF2BP2 is notable for its persistent expression in a variety of organs, including the heart, throughout adulthood.

This research looks at how IGF2BP2 reacts in cardiomyocytes during times of cardiac stress and remodeling. Researchers discovered an increase in IGF2BP2 expression under stress, followed by a return to normal levels after cardiac recovery. This pattern encouraged researchers to look into the potential adaptive role of IGF2BP2 in cardiac stress management.

Using an inducible mouse strain with increased IGF2BP2 expression, researchers discovered an unexpected result: increased IGF2BP2 expression causes dilated cardiomyopathy (DCM) of the heart and eventual mortality in both infants and adults within 3-4 weeks. However, if transgenic expression was reduced within two weeks, there was a rescue effect. None of the mice perished, and they recovered completely within 12 weeks, demonstrating that this disease is reversible.

Further examination of hearts with elevated IGF2BP2 levels indicated significant alterations in sarcomeric and mitochondrial proteins. These hearts, in particular, have fragmented mitochondria and stretched, thinner sarcomeres, offering light on the underlying mechanisms that contribute to DCM.

Importantly, the researchers discovered elevated levels of IGF2BP2 in individuals with DCM or myocardial infarction, implying clinical importance and the possibility of targeted treatment interventions.

The prevalence of DCM is unknown, but it has been estimated to be as high as one in every 250 persons. Prof. Joel Yisraeli of the Institute for Medical Research-Israel-Canada at Hebrew University, the project’s principal investigator, stated, “These findings reveal a previously unknown role for IGF2BP2 in stress-induced cardiomyopathy, paving the way for innovative therapeutic strategies in managing heart conditions.” The findings were recently published in Communications Biology, a Nature Portfolio journal, with Dr. Miriam Krumbein as lead author, as part of a collaborative effort between the Yisraeli lab at the Institute for Medical Research – Israel-Canada at the Hebrew University of Jerusalem and Prof. Sonja Kessler of Martin-Luther University Halle-Wittenburg.

This research highlights IGF2BP2’s potential as a promising therapeutic target for a variety of cardiomyopathies. The team’s findings open up new routes for research and potential treatment advances, bringing hope to those suffering from heart disease.

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