BIOSYNTHETIC PLATFORM FOR CARDIOPROTECTIVE GENE EXPRESSION USING NEONATAL IMMATURE AND FETAL HEART TISSUE

摘要

The present invention is directed toward elucidation of a human fetal gene expression program in response to simulated ischemia/reperfusion (I/R) in order to identify molecular targets which account for the innate cardioprotection exhibited by the fetal phenotype. The present invention is further directed toward identification of cardioprotective gene programs in the neonatal heart. Specifically, the newborn (immature) heart or alternatively fetal heart has been recognized as having an increased resistance to pathophysiological forms of stress, e.g., hypoxic stress. The pattern of gene expression in immature heart subject to naturally occurring hemodynamic and hypoxic stress, e.g., that associated with obstructive congenital heart disease, is herein revealed by differential gene profiling; and the induction of a cardioprotective, gene pattern, and particularly useful subsets thereof, in the heart chronically adapted to stress is confirmed. Thus, the chronically stressed immature heart provides a novel biosynthetic platform for cardioprotective gene expression, useful as a basis for the development of diagnostic and therapeutic modalities.