© 1995 American Heart Association, Inc.
Articles |
Apoptosis (Programmed Cell Death) in Arteries of the Neonatal Lamb
From the Banting and Best Diabetes Centre, The Toronto Hospital Research Institute, and the Department of Pathology, University of Toronto, Ontario, Canada.
Correspondence to B. Lowell Langille, PhD, The Toronto Hospital Research Institute, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada.
Abstract 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.
Key Words: cell suicide • physiological cell death • arterial remodeling
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|
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|
|
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|
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|
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|
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|
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|
|
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|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
J. Diez, A. Panizo, M. Hernandez, and J. Pardo Is the Regulation of Apoptosis Altered in Smooth Muscle Cells of Adult Spontaneously Hypertensive Rats? Hypertension, March 1, 1997; 29(3): 776 - 780. [Abstract] [Full Text]
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|
|
|
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D. deBlois, B.-S. Tea, T.-V. Dam, J. Tremblay, and P. Hamet Smooth Muscle Apoptosis During Vascular Regression in Spontaneously Hypertensive Rats Hypertension, January 1, 1997; 29(1): 340 - 344. [Abstract] [Full Text] [PDF]
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P. L. Jones and M. Rabinovitch Tenascin-C Is Induced With Progressive Pulmonary Vascular Disease in Rats and Is Functionally Related to Increased Smooth Muscle Cell Proliferation Circ. Res., December 1, 1996; 79(6): 1131 - 1142. [Abstract] [Full Text]
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|
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M. J. Pollman, T. Yamada, M. Horiuchi, and G. H. Gibbons Vasoactive Substances Regulate Vascular Smooth Muscle Cell Apoptosis: Countervailing Influences of Nitric Oxide and Angiotensin II Circ. Res., October 1, 1996; 79(4): 748 - 756. [Abstract] [Full Text]
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|
|