Incorrectly Spliced RNA Could Lead to Diabetic Cardiomyopathy

Elevated levels of RBFOX2 found in diabetic heart tissue could cause heart damage.

Researchers discovered a molecular mechanism involved in heart damage from diabetes.

The risk of developing cardiovascular disease in patients with diabetes is 2 to 5 times higher. Diabetic cardiomyopathy is a disorder of the heart muscle, which can result in heart failure.

Molecular mechanisms that cause this disorder are not well understood, according to the study published in Cell Reports. In a prior study, researchers found that RNA splicing is not properly regulated.

It also revealed elevated levels of the splicing regulator RBFOX2 in patients with diabetes. In the current study, researchers analyzed how the regulation of RBFOX2 adds to splicing defects and how these defects impact cardiac function.

Researchers discovered that RBFOX2 binds to 73% of incorrectly spliced RNA in heart tissues. This splicing was seen to diminish normal gene expression that effects molecular metabolism, programmed cell death, protein trafficking, and calcium handling that is critical for regulating the heartbeat.

"We discovered that RBFOX2 function is disrupted in diabetic hearts before cardiac complications are noticeable and RBFOX2 dysregulation contributes to abnormal calcium signaling in the heart," concluded lead study author N. Muge Kuyumcu-Martinez, PhD. "Identifying RBFOX2 as an important contributor to diabetic complications and learning how it is dysregulated may allow us to develop new tools to diagnose, prevent or treat diabetic cardiomyopathy in the future."

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