CARDIOLOGY
Fish and humans have similar circulatory systems. Molecular biologist Christian Mosimann, PhD, and team can color-code them to understand how they develop.
Circulating Cast
Q: What can aquarium sealant, fish embryos and immune cells tell researchers about pediatric heart failure?
Pediatric heart disease is rare and heterogenous, which makes it difficult to study. Across several labs at Children’ s Hospital Colorado and the Anschutz Medical Campus, teams of researchers, many of them post-doctorate and junior faculty, are investigating the early heart from an ever-growing array of angles.
Pediatric cardiologist Stephanie Nakano, MD, is gluing a heart cell to a machine. The cell came from a tissue bank of diseased hearts taken, with consent, from nearly every patient who gets a heart transplant at Children’ s Colorado. The glue is regular old aquarium sealant, the kind you can get at a pet store.
Dr. Nakano first isolates the individual heart muscle cells. Under a microscope, she can identify the proteins that make them contact. Then she aligns the cell with the needle tips of the machine and pilots a pair of motorized micropositioners to either end of the cell. She’ ll need to make it happen inside of three minutes, before the glue starts to cure.
“ It’ s a pretty delicate technique,” she says.“ It took me a long time to learn.”
Once attached, the machine will measure the precise amount of contractile force this particular cell can generate. The technique itself has been around nearly 50 years, and it’ s been used to generate a lot of mechanical data about adult heart cells, giving rise to treatments that have led to vastly better outcomes in many forms of adult heart failure.
But those medications don’ t work as well in kids, even for the same conditions.
Comparing the cells of kids with dilated cardiomyopathy with the literature on their adult counterparts, Dr. Nakano, along with her mentor, pediatric cardiologist Shelly Miyamoto, MD, is making progress understanding why.
“ We found some similarities between pediatric and adult patients in the failing phenotype, but also differences,” Dr. Nakano says.“ The amount of calcium it takes to make the cells contract is similar, but the amount of cooperativity between these filament proteins is less, meaning it’ s more difficult for the necessary proteins to bind( 1). That hints at differences at the protein level.”
Understanding those differences could eventually help researchers develop new drugs, or figure out ways to tweak existing drugs, to increase their effectiveness in kids. It’ s just one way into the deep and complex web of problems that can affect a child’ s heart.
“ We’ re trying to understand these problems, but we’ re also investing in these researchers,” Dr. Miyamoto says.“ I was a junior researcher when we started this whole thing, and the idea is that it’ s constant turnover and growth. Leadership evolves. Projects evolve. Different labs branch off and become independent. It’ s complementary and collaborative.”
8 | CHILDREN’ S HOSPITAL COLORADO