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March 2010 Issue

The research team of (from left to right) Xiaowei Zhang, PhD, Guo-Chang Fan, PhD, Solange Abbate and Xiaohong Wang, MD, hope that their findings will ­­be used to stop health problems from ever developing.
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Micro Elements May Help Heart in Big Way

By Katie Pence
Published March 2010

You’ve heard it before: It’s the small things that count.

Usually, the saying is applied to simple acts of kindness done for a person by their significant other, a friend or family member.

But Guo-Chang Fan, PhD, says it also applies to mechanisms in the body and ways that disease could be prevented by examining them more closely.

Fan, an assistant professor of pharmacology and cell biophysics, and his research team, including Xiaohong Wang, MD, Xiaowei Zhang, PhD, and Solange Abbate, are looking at some of the smallest elements of biological systems to discover cellular therapies that may stop many of the most serious health problems from ever developing.

Since 2007, Fan and his team have been studying the role of microRNAs—recently discovered small, non-coding RNAs that control multiple biological functions through regulation of thousands of cellular proteins in the body—in mice models and in cultures.

Their research has produced results that could one day leave the human heart better protected during a heart attack.

"MicroRNA-320 is of particular interest because our findings indicate that microRNA-320 makes the heart more sensitive to ischemic injury, or heart attack,” Fan says. "Thus, by lowering the number of microRNA-320 that gets to the heart, we can protect it from cardiac injury.”

According to Fan’s research published in the April 20, 2009, edition of the journal Circulation, blocking this specific strand of microRNA resulted in a 60 percent decrease in damage.

"We applied antagomirs—a chemically engineered nucleotide which is used to inactivate RNA— to prevent microRNA-320 from being produced,” he says.

Fan’s findings have earned him several awards including the American Heart Association’s (AHA) Outstanding Early Career Investigator Award, the AHA’s 2009 Elected Fellow award and a travel grant award for the 2009 AHA annual conference.

"There are very few companies worldwide that are doing the kind of research we are doing at the University of Cincinnati,” he says. "Our research has the potential to impact patient care tremendously by creating a therapy that could prevent heart damage and save lives.”

Fan says the next step is investigating the wide array of microRNA and their differing effects on the heart.

Abbate, a research technician in Fan’s lab, says that the effects of microRNA have been linked to other diseases as well, such as cancer, neurological illnesses and kidney disease.

"Despite how much is still unknown in these fields, a better understanding of microRNAs has an enormous clinical potential for treating diseases with some of the highest mortality rates,” she says.

"The research is far from complete, but the discoveries will lead to the development of treatments that could save thousands of lives.” 

More Research May Lead to Heart Treatments
Guo-Chang Fan, PhD, is working with several other cellular mechanisms that could one day lead 
to the creation of treatment for heart conditions.

Fan, along with colleagues in pharmacology and cell biophysics, recently published studies discovering potential ways to make stem cells survive longer in the heart and to prevent cardiac-induced sepsis, or full-body infection that often leads to death.

In the Sept. 18, 2009, issue of the journal Stem Cells, Fan and colleagues reported that by genetically engineering mesenchymal (multi-potent) stem cells and adding protein Hsp20, the cells became more stress resistant, keeping them alive and functioning in the heart for a longer period of time.

A second study, published June 6, 2009, in the online issue of the Journal of Molecular and Cellular Cardiology, shows that an increase in the same protein can protect against cardiac cell death in mouse models with sepsis. 

These are both basic research studies that were completed in animal models. Fan says there are plans to further investigate ways that Hsp20 can be used to improve cardiac function with hopes of creating new cellular therapies for humans.

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