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Frozen pediatric cardiac tissue samples are stored and processed by the Core Lab for Translational and Clinical Research in the Preston Research Building. (photo by Jeni Slone)

Tissue bank aims to help solve heart disease mysteries

BY: MIMI ECKHARD

9/15/2011 - Each year Vanderbilt surgeons perform surgery on 500 of the tiniest patients to correct heart defects.

In the past, portions of excess heart tissue from these procedures were discarded. But Vanderbilt recognized the value in these tissues, which could hold answers to congenital heart defects in infants and children.

One of only a handful of such repositories in the U.S., the Vanderbilt Pediatric Cardiac Tissue Repository enables surgeons, physicians and researchers to work together in understanding why certain heart defects occur and how they can be more accurately treated.

“Having access to this valuable tissue is critical in developing innovative new treatments for our patients,” said David Bichell, M.D., chief of Pediatric Cardiac Surgery, who spearheaded this multi-disciplinary collaborative initiative.

The samples are processed and stored by the Core Lab for Translational and Clinical Research in the Division of Cardiovascular Medicine, under the direction of Yan Ru Su, M.D.

“Dr. Bichell’s commitment to this effort has provided us all with a vital resource to study the molecular mechanism of congenital heart disease and then apply this knowledge to patient care,” said Su.

As of August, the repository has collected 25 explanted hearts following heart transplants and 27 surgical tissue specimens, along with serum and DNA that can be used for biomarker and genetic studies.

H. Scott Baldwin, M.D., chief of Pediatric Cardiology, has been studying why certain heart valves don’t fully open, affecting the heart’s overall function. Two million people in the U.S. suffer from this condition.

Armed with valve tissue from the pediatric repository, Baldwin and his lab are studying the proteins in these tissues, which are the building blocks of each cell’s ultimate structure and function. By examining these proteins, Baldwin hopes to gain a stronger understanding of why these valves deteriorate in the first place.

“Our goal is to develop alternative therapies that reduce the need for surgery in these children,” said Baldwin, the Katrina Overall McDonald Chair in Pediatrics and co-director of the Pediatric Heart Institute.

By using imaging technology, Richard Caprioli, M.D., professor of Biochemistry and director of Mass Spectometry, has joined Baldwin in determining what proteins are involved in the valve’s mutation.

Peggi Angel, Ph.D., a former post-doctoral fellow with Caprioli and Baldwin, was recently awarded a scholarship from the Vanderbilt Institute for Clinical and Translational Research to continue the work she began during her fellowship.

As a research instructor, she is working with Caprioli and Baldwin to understand what proteins are involved in the defective valve structure and how protein expression contributes to normal valve development.

These studies will help pinpoint critical proteins as potential targets for treating pediatric valve disease, and will help shed light on how valves grow, which could lead to the development of replacement valves for children.

“None of this was possible before the cardiac tissue bank,” said Angel. “We can now delve deeper into the disease and truly improve patient care,” she said.

In addition to these studies, Charles Hong, M.D., assistant professor of Cardiovascular Medicine, is spearheading genetic and stem cell studies on heart tissue and blood samples from families with multiple instances of congenital defects.

“There is so much to learn about the fundamental causes of congenital diseases,” said Hong. “The heart tissue repository gives us the rare opportunity to look for root causes of congenital heart disease within genes and heart tissues from actual patients,” he said.

The Pediatric Cardiac Tissue Repository is affiliated with the Vanderbilt Heart & Vascular Institute’s Main Heart Registry and Bio-Repository, which was established in late 2009 to obtain and store heart tissue samples for use in genetic studies.

With the support of a Vanderbilt Institute for Clinical and Translational Research (VICTR) grant, Tarek Absi, M.D., assistant professor of Cardiac Surgery, and Su are using the Bio-Repository to predict how patients with mitral valve disease will respond to current treatment, both medical and surgical, and to identify novel molecular targets for new treatment.

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