The proper development and growth of the fetal heart is essential to the health of the growing fetus. Eventhough we have some understanding of the development and subsequent growth of the mammalian heart,the mechanisms underlying fetal cardiac growth are not well understood. Our laboratory has a long-standingnterest in fetal cardiac growth. We have found that fetal cardiac function is different during pressureoverload or volume overload. We have also found that fetal cardiac myocytes undergo different rates ofterminal differentiation when exposed to increased pressure or to increased volume load. We havediscovered that hyperplasia and hypertrophy are not directly temporally linked in the growing fetal heart.These discoveries are important because these growth mechanisms are different from those of the adult andbecause the heart uses the anatomic configuration it develops as a fetus for life. Project II will furtherexplore the relationship between cardiac function and growth by pursuing the following Specific Aims:
Specific Aim 1 (Cardiac Function): to assess fetal cardiovascular function during systolic load modulatedgrowth. Functional adaptation of the fetal heart to systolic load likely allows the fetus to maintain adequateblood flow to the fetal systemic and fetal placental circulations maintaining the well being of the fetus.
Specific Aim 2 (Cardiac Growth): to determine the relative contribution and timing of hyperplasia andhypertrophy in conditions of increased systolic pressure load and reduced systolic pressure load. Growth ofthe fetal heart is likely dependent on a load driven balance of myocyte hyperplasia, hypertrophy and terminaldifferentiation.
Specific Aim 3 (In Vivo Cardiac Myocyte Signaling): to determine the role of the MAP Kinase signalingcascade in hyperplasia and hypertrophy in response to increased or decreased cardiac load. Myocardialtissue from hearts exposed to normal, increased or decreased systolic load will be studied. Mechanical loadinduced fetal cardiac growth is likely mediated by the MAP kinase signaling cascade.Superimposed on the genetic instructions for developing cardiac chamber form are hemodynamic clues,which determine the rate of growth and function of the fetal heart. Understanding the mechanisms of cardiacgrowth and terminal differentiation during the fetal period will provide important insight into thepathophysiological processes affecting the adult heart in later life.
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