Apoptosis (programmed cell death) in arteries of the neonatal lamb.
We have examined whether cell death contributes to postnatal remodeling of arteries in lambs. First, abdominal aortic smooth muscle cell proliferation rates fell from 2.87 +/- 0.08% per day at 3 days of age to 1.75 +/- 0.15% per day at 21 days. These proliferation rates would yield a 50% increase in DNA content in the absence of cell death. No increase in DNA content was observed (P < .05 for predicted versus measured accumulation); therefore, significant cell death was inferred. The same analysis did not indicate high cell-death rates in the carotid, renal, or iliac arteries; however, cell death was detected in situ by end-labeling partially degraded DNA with terminal deoxynucleotidyl transferase or by nuclear labeling with propidium iodide, a fluorescent dye that permeates only nonviable cells. Nuclei were labeled in all arteries, although labeling was most frequent in the abdominal aorta, a vessel that regresses substantially after birth. Cell death was apoptotic because DNA extracted from arteries and end-labeled with [32P]dCTP produced a series of low molecular weight bands (DNA ladder) on an agarose gel, a hallmark of apoptosis. The ladder was strong for neonatal abdominal aorta but weak for other arteries. Only weak laddering was observed for fetal abdominal aortas in late gestation, confirming that high apoptosis rates in this vessel were initiated after birth. Intense DNA ladders and frequent in situ labeling indicated high rates of apoptosis in the postnatal intra-abdominal umbilical artery, another vessel that regresses after birth. We conclude that apoptosis contributes to postpartum arterial remodeling. This contribution is greatest in arteries that regress after birth.
Banting and Best Diabetes Centre, Toronto Hospital Research Institute, Ontario, Canada.
A
A
Cho
D W
DW
Courtman
B L
BL
Langille
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D017209:Apoptosis; D001158:Arteries / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D002455:Cell Division; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D012756:Sheep
D004247:DNA