Tain-Yen Hsia, MD

Extracellular Mechanisms in Pediatric Cardiomyopathy
Medical University of South Carolina, Charleston, SC
Tain-Yen Hsia, MD – $50,000

The extracellular matrix is an integral part of the heart. It provides the scaffolding upon which the cells of the heart can build healthy architecture and structure that are essential for normal heart functions. Abnormal maintenance of the extracellular matrix has been known to result in clinical manifestations of various forms of heart failure in adults but little is known about it's effect on children. In the heart, the regulation of extracellular matrix belongs to a set of enzymes called matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Maintaining a delicate balance between these two groups of enzymes controls the extracelluar matrix content and thus heart function. The goal of this pilot study is to better understand the role that MMPs and TIMPs play in various pediatric cardiomyopathies, to examine differences from adult cardiomyopathy, and to develop a way to measure these enzymes from small blood samples. As a pilot study, we will focus our initial efforts on the elucidation of the role of extracellular matrix in idiopathic dilated cardiomyopathy by examining the tissue and serum MMPs and TIMP in children afflicted with this disease through biopsies, explanted heart, and stored samples in the Pediatric Cardiomyopathy Registry/Repository. By showing a direct relationship between heart failure severity and MMP and TIMP enzyme levels, biomarkers can be identified to predict the advent of heart failure and the progression of the disease, perhaps even before symptoms appear. If this methodology is proven safe and efficacious in infants and small children, it can be used to screen patients from high-risk families or backgrounds. New drugs that can modulate the extracellular matrix by re-balancing the MMP and TIMP system may be developed to prevent or improve symptoms of end stage heart failure.