© 2000 American Heart Association, Inc.
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Apoptosis During Cardiovascular Development
From the Departments of Medicine and Physiology, Case Western Reserve School of Medicine (S.A.F.), Cleveland, Ohio; Department of Laboratory Medicine and Pathobiology (B.L.L.), University of Toronto and Toronto General Hospital, Toronto, Canada; and Departments of Pediatric Cardiology and Molecular Biology (D.S.), University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to B. Lowell Langille, Toronto General Hospital, University Health Network, 200 Elizabeth St, CCRW 1-836, Toronto, M5G 2C4, Canada. E-mail langille{at}uhnres.utoronto.ca
Abstract—Morphogenesis and developmental remodeling of cardiovascular tissues involve coordinated regulation of cell proliferation and apoptosis. In the heart, clear evidence points toward focal apoptosis as a contributor to development of the embryonic outflow tract, cardiac valves, conducting system, and the developing coronary vasculature. Apoptosis in the heart is likely regulated by survival and death signals that are also present in many other tissues. Cell type–specific regulation may be superimposed on general cell death/survival machinery through tissue-specific transcriptional pathways. In the vasculature, apoptosis almost certainly contributes to developmental vessel regression, and it is of proven importance in remodeling of arterial structure in response to local changes in hemodynamics. Physical forces, growth factors, and extracellular matrix drive vascular cell survival pathways, and considerable evidence points to local nitric oxide production as an important but complex regulator of vascular cell death. In both the heart and vasculature, progress has been impeded by inadequate information concerning the incidence of apoptosis, its relative importance compared with the diverse cell behaviors that remodel developing tissues, and by our primitive knowledge concerning regulation of cell death in these tissues. However, tools are now available to better understand apoptosis in normal and abnormal development of cardiovascular structures, and a framework has been established that should lead to considerable progress in the coming years.
Key Words: apoptosis • development • myocardium • smooth muscle • endothelium
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