© 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
This article has been cited by other articles:
 |
|
 |
|
  M. C.H. Clarke, T. D. Littlewood, N. Figg, J. J. Maguire, A. P. Davenport, M. Goddard, and M. R. Bennett Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration Circ. Res., June 20, 2008; 102(12): 1529 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nishimura, W. Li, Y. Hoshino, T. Kadohama, H. Asada, S. Ohgi, and B. E. Sumpio Role of AKT in cyclic strain-induced endothelial cell proliferation and survival Am J Physiol Cell Physiol, March 1, 2006; 290(3): C812 - C821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Safar and H. S. Boudier Vascular Development, Pulse Pressure, and the Mechanisms of Hypertension Hypertension, July 1, 2005; 46(1): 205 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Langille and D. Dajnowiec Cross-Linking Vasomotor Tone and Vascular Remodeling: A Novel Function for Tissue Transglutaminase? Circ. Res., January 7, 2005; 96(1): 9 - 11. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kiyono and M. Shibuya Bone Morphogenetic Protein 4 Mediates Apoptosis of Capillary Endothelial Cells during Rat Pupillary Membrane Regression Mol. Cell. Biol., July 1, 2003; 23(13): 4627 - 4636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Taurin, V. Seyrantepe, S. N. Orlov, T.-L. Tremblay, P. Thibault, M. R. Bennett, P. Hamet, and A. V. Pshezhetsky Proteome Analysis and Functional Expression Identify Mortalin as an Antiapoptotic Gene Induced by Elevation of [Na+]i/[K+]i Ratio in Cultured Vascular Smooth Muscle Cells Circ. Res., November 15, 2002; 91(10): 915 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Durand, Z. Mallat, F. Addad, F. Vilde, M. Desnos, C. Guerot, A. Tedgui, and A. Lafont Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1680 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Jackson, A. I. Gotlieb, and B. L. Langille Wall Tissue Remodeling Regulates Longitudinal Tension in Arteries Circ. Res., May 3, 2002; 90(8): 918 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. M. Hassan, I. M. Lang, M. Ignatescu, R. Ullrich, D. Bonderman, P. Wexberg, F. Weidinger, and H. D. Glogar Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1333 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Intengan and E. L. Schiffrin Vascular Remodeling in Hypertension: Roles of Apoptosis, Inflammation, and Fibrosis Hypertension, September 1, 2001; 38(3): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Stadler, J. Phillips, Y. Toyoda, M. Federman, S. Levitsky, and J. D. McCully Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion Ann. Thorac. Surg., August 1, 2001; 72(2): 555 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sho, M. Sho, T. M. Singh, C. Xu, C. K. Zarins, and H. Masuda Blood Flow Decrease Induces Apoptosis of Endothelial Cells in Previously Dilated Arteries Resulting From Chronic High Blood Flow Arterioscler. Thromb. Vasc. Biol., July 1, 2001; 21(7): 1139 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Fisher, B. L. Langille, and D. Srivastava Apoptosis During Cardiovascular Development Circ. Res., November 10, 2000; 87(10): 856 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Walsh, R. C. Smith, and H.-S. Kim Vascular Cell Apoptosis in Remodeling, Restenosis, and Plaque Rupture Circ. Res., August 4, 2000; 87(3): 184 - 188. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Tricot, Z. Mallat, C. Heymes, J. Belmin, G. Leseche, and A. Tedgui Relation Between Endothelial Cell Apoptosis and Blood Flow Direction in Human Atherosclerotic Plaques Circulation, May 30, 2000; 101(21): 2450 - 2453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Chan, L. Hegyi, S. Scott, N. R. B. Cary, P. L. Weissberg, and M. R. Bennett Sensitivity to Fas-Mediated Apoptosis Is Determined Below Receptor Level in Human Vascular Smooth Muscle Cells Circ. Res., May 26, 2000; 86(10): 1038 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Kim, K.-K. Hwang, J.-W. Seo, S.-Y. Kim, B.-H. Oh, M.-M. Lee, and Y.-B. Park Apoptosis and Regulation of Bax and Bcl-X Proteins During Human Neonatal Vascular Remodeling Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 957 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. H. Schiffers, D. Henrion, C. M. Boulanger, E. Colucci-Guyon, F. Langa-Vuves, H. van Essen, G. E. Fazzi, B. I. Levy, and J. G. R. De Mey Altered Flow-Induced Arterial Remodeling in Vimentin-Deficient Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 611 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L van Heerde, S. Robert-Offerman, E. Dumont, L. Hofstra, P. A Doevendans, J. F.M Smits, M. J.A.P Daemen, and C. P.M Reutelingsperger Markers of apoptosis in cardiovascular tissues: focus on Annexin V Cardiovasc Res, February 1, 2000; 45(3): 549 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Perlman, M. Sata, K. Krasinski, T. Dorai, R. Buttyan, and K. Walsh Adenovirus-encoded hammerhead ribozyme to Bcl-2 inhibits neointimal hyperplasia and induces vascular smooth muscle cell apoptosis Cardiovasc Res, February 1, 2000; 45(3): 570 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M Kockx and A. G Herman Apoptosis in atherosclerosis: beneficial or detrimental? Cardiovasc Res, February 1, 2000; 45(3): 736 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. McCarthy and M. Bennett The regulation of vascular smooth muscle cell apoptosis Cardiovasc Res, February 1, 2000; 45(3): 747 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kamenz, W. Seibold, M. Wohlfrom, S. Hanke, N. Heise, C. Lenz, and H. Hanke Incidence of intimal proliferation and apoptosis following balloon angioplasty in an atherosclerotic rabbit model Cardiovasc Res, February 1, 2000; 45(3): 766 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Holm, C. B. Andersen, S. Haunso, and P. Riis Hansen ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries Cardiovasc Res, February 1, 2000; 45(3): 777 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Imamura, T. Nishikawa, E. Hiratsuka, A. Takao, and R. Matsuoka Behavior of Smooth Muscle Cells during Arterial Ductal Closure at Birth J. Histochem. Cytochem., January 1, 2000; 48(1): 35 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Hayakawa, G. Takemura, J. Misao, M. Kanoh, M. Ohno, H. Ohashi, H. Takatsu, H. Ito, K. Fukuda, T. Fujiwara, et al. Apoptosis and Overexpression of Bax Protein and bax mRNA in Smooth Muscle Cells Within Intimal Hyperplasia of Human Radial Arteries : Analysis With Arteriovenous Fistulas Used for Hemodialysis Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2066 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L Shovlin and M. Letarte Rare diseases bullet 4: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms Thorax, August 1, 1999; 54(8): 714 - 729. [Full Text]
|
|
|
|
|
|
M. Aoki, R. Morishita, H. Matsushita, S.-i. Hayashi, H. Nakagami, K. Yamamoto, A. Moriguchi, Y. Kaneda, J. Higaki, and T. Ogihara Inhibition of the p53 Tumor Suppressor Gene Results in Growth of Human Aortic Vascular Smooth Muscle Cells : Potential Role of p53 in Regulation of Vascular Smooth Muscle Cell Growth Hypertension, August 1, 1999; 34(2): 192 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Bayer, S. L. Adamson, and B. L. Langille Atrophic Remodeling of the Artery-Cuffed Artery Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1499 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Pollman, L. Naumovski, and G. H. Gibbons Vascular Cell Apoptosis : Cell Type–Specific Modulation by Transforming Growth Factor-ß1 in Endothelial Cells Versus Smooth Muscle Cells Circulation, April 20, 1999; 99(15): 2019 - 2026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-Y. Wang, H.-K. V. Ho, P. S. Lin, S. P. Schwarzacher, M. J. Pollman, G. H. Gibbons, P. S. Tsao, and J. P. Cooke Regression of Atherosclerosis : Role of Nitric Oxide and Apoptosis Circulation, March 9, 1999; 99(9): 1236 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R Bennett Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture Cardiovasc Res, February 1, 1999; 41(2): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Henderson, Y.-J. Geng, G. K. Sukhova, A. D. Whittemore, J. Knox, and P. Libby Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms Circulation, January 12, 1999; 99(1): 96 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Courtman, A. Cho, L. Langille, and G. J. Wilson Eliminating Arterial Pulsatile Strain by External Banding Induces Medial but Not Neointimal Atrophy and Apoptosis in the Rabbit Am. J. Pathol., December 1, 1998; 153(6): 1723 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kockx Apoptosis in the Atherosclerotic Plaque : Quantitative and Qualitative Aspects Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1519 - 1522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang and J. A. Keiser Molecular characterization of rabbit CPP32 and its function in vascular smooth muscle cell apoptosis Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1132 - H1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kondo, N. Hashimoto, H. Kikuchi, F. Hazama, I. Nagata, H. Kataoka, and W. I. Rosenblum Apoptosis of Medial Smooth Muscle Cells in the Development of Saccular Cerebral Aneurysms in Rats • Editorial Comment Stroke, January 1, 1998; 29(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsushita, R. Morishita, I. Kida, M. Aoki, S.-i. Hayashi, N. Tomita, K. Yamamoto, A. Moriguchi, A. Noda, Y. Kaneda, et al. Inhibition of Growth of Human Vascular Smooth Muscle Cells by Overexpression of p21 Gene Through Induction of Apoptosis Hypertension, January 1, 1998; 31(1): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Bennett, T. D. Littlewood, S. M. Schwartz, and P. L. Weissberg Increased Sensitivity of Human Vascular Smooth Muscle Cells From Atherosclerotic Plaques to p53-Mediated Apoptosis Circ. Res., October 19, 1997; 81(4): 591 - 599. [Abstract] [Full Text]
|
|
|
|
|
|
E. J. R. Mattsson, T. R. Kohler, S. M. Vergel, and A. W. Clowes Increased Blood Flow Induces Regression of Intimal Hyperplasia Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2245 - 2249. [Abstract] [Full Text]
|
|
|
|
|
|
A. Cho, L. Mitchell, D. Koopmans, and B. L. Langille Effects of Changes in Blood Flow Rate on Cell Death and Cell Proliferation in Carotid Arteries of Immature Rabbits Circ. Res., September 19, 1997; 81(3): 328 - 337. [Abstract] [Full Text]
|
|
|
|
|
|
L. A. Kirshenbaum and D. de Moissac The bcl-2 Gene Product Prevents Programmed Cell Death of Ventricular Myocytes Circulation, September 2, 1997; 96(5): 1580 - 1585. [Abstract] [Full Text]
|
|
|
|
|
|
P. Moreau, B.-S. Tea, T.-V. Dam, and P. Hamet Altered Balance Between Cell Replication and Apoptosis in Hearts and Kidneys of Newborn SHR Hypertension, September 1, 1997; 30(3): 720 - 724. [Abstract] [Full Text]
|
|
|
|
|
|
J. Slomp, A. C. Gittenberger-de Groot, M. A. Glukhova, J. C. van Munsteren, M. M. Kockx, S. M. Schwartz, and V. E. Koteliansky Differentiation, Dedifferentiation, and Apoptosis of Smooth Muscle Cells During the Development of the Human Ductus Arteriosus Arterioscler. Thromb. Vasc. Biol., May 1, 1997; 17(5): 1003 - 1009. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. deBlois, S.M. Schwartz, E.M. van Kleef, J.E. Su, K.A. Griffin, A.K. Bidani, M.J.A.P. Daemen, and D.M. Lombardi Chronic {alpha}1-Adrenoreceptor Stimulation Increases DNA Synthesis in Rat Arterial Wall: Modulation of Responsiveness After Vascular Injury Arterioscler. Thromb. Vasc. Biol., September 1, 1996; 16(9): 1122 - 1129. [Abstract] [Full Text]
|
|
|
|
|
|
D. deBlois, M. Viswanathan, J.E. Su, A.W. Clowes, J.M. Saavedra, and S.M. Schwartz Smooth Muscle DNA Replication in Response to Angiotensin II Is Regulated Differently in the Neointima and Media at Different Times After Balloon Injury in the Rat Carotid Artery: Role of AT1 Receptor Expression Arterioscler. Thromb. Vasc. Biol., September 1, 1996; 16(9): 1130 - 1137. [Abstract] [Full Text]
|
|
|
|
|
|
P. Hamet Cancer and Hypertension: An Unresolved Issue Hypertension, September 1, 1996; 28(3): 321 - 324. [Full Text]
|
|
|
|
 |
|
 J. C. Fox and J. R. Shanley Antisense Inhibition of Basic Fibroblast Growth Factor Induces Apoptosis in Vascular Smooth Muscle Cells J. Biol. Chem., May 24, 1996; 271(21): 12578 - 12584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Y. Wong and B. L. Langille Developmental Remodeling of the Internal Elastic Lamina of Rabbit Arteries : Effect of Blood Flow Circ. Res., May 1, 1996; 78(5): 799 - 805. [Abstract] [Full Text]
|
|
|
|
|
|
M.R. Bennett, D.F. Gibson, S.M. Schwartz, and J.F. Tait Binding and Phagocytosis of Apoptotic Vascular Smooth Muscle Cells Is Mediated in Part by Exposure of Phosphatidylserine Circ. Res., December 1, 1995; 77(6): 1136 - 1142. [Abstract] [Full Text]
|
|
|
|
|
|
M. R. Bennett, G. I. Evan, and S. M. Schwartz Apoptosis of Rat Vascular Smooth Muscle Cells Is Regulated by p53-Dependent and -Independent Pathways Circ. Res., August 1, 1995; 77(2): 266 - 273. [Abstract] [Full Text]
|
|
|
|
|
|
Z. S. Jackson, A. I. Gotlieb, and B. L. Langille Wall Tissue Remodeling Regulates Longitudinal Tension in Arteries Circ. Res., May 3, 2002; 90(8): 918 - 925. [Abstract] [Full Text] [PDF]
|
|