Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
Circulation Research. 2000;87:434-439

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dimmeler, S.
Right arrow Articles by Zeiher, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dimmeler, S.
Right arrow Articles by Zeiher, A. M.
Related Collections
Right arrow Angiogenesis
Right arrow Apoptosis
Right arrow Mechanism of atherosclerosis/growth factors
Right arrow Other Vascular biology
(Circulation Research. 2000;87:434.)
© 2000 American Heart Association, Inc.


MiniReview

Endothelial Cell Apoptosis in Angiogenesis and Vessel Regression

Stefanie Dimmeler, Andreas M. Zeiher

From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.

Correspondence to Stefanie Dimmeler, PhD, Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Dimmeler{at}em.uni-frankfurt.de

Abstract—The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. In the past few years, compelling evidence accumulated that dysregulation of apoptosis can lead to embryonal death and is involved in the pathophysiology of various inflammatory and degenerative diseases. Specifically, the occurrence of endothelial cell apoptosis has deleterious effects on the development of the cardiovascular system leading to embryonal death. Moreover, endothelial cell apoptosis counteracts neovascularization in the adult organism. On the basis of these findings, one may consider the regulation of endothelial cell apoptosis as a potential therapeutic target. The induction of endothelial cell apoptosis may limit unwanted neovascularization of tumors. In contrast, the prevention of endothelial cell apoptosis may improve angiogenesis and vasculogenesis in patients with ischemia. The present work critically reviews the existing data that supports a role of endothelial cell apoptosis for vascular growth and remodeling and provides insights into the mechanisms and the potential therapeutic consequences.


Key Words: cell death • endothelial cells • growth factors • hemodynamic forces




This article has been cited by other articles:


Home page
Am. J. Physiol. Cell Physiol.Home page
S. Kondo, Y. Tang, E. A. Scheef, N. Sheibani, and C. M. Sorenson
Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1521 - C1530.
[Abstract] [Full Text] [PDF]


Home page
J. Lipid Res.Home page
E. Soupene, V. Serikov, and F. A. Kuypers
Characterization of an acyl-coenzyme A binding protein predominantly expressed in human primitive progenitor cells
J. Lipid Res., May 1, 2008; 49(5): 1103 - 1112.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
N. Matsuda, Y. Takano, S.-i. Kageyama, N. Hatakeyama, K. Shakunaga, I. Kitajima, M. Yamazaki, and Y. Hattori
Silencing of caspase-8 and caspase-3 by RNA interference prevents vascular endothelial cell injury in mice with endotoxic shock
Cardiovasc Res, October 1, 2007; 76(1): 132 - 140.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
M. Artwohl, K. Muth, K. Kosulin, R. de Martin, T. Holzenbein, G. Rainer, A. Freudenthaler, N. Huttary, L. Schmetterer, W. K. Waldhausl, et al.
R-(+)-{alpha}-lipoic acid inhibits endothelial cell apoptosis and proliferation: involvement of Akt and retinoblastoma protein/E2F-1
Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E681 - E689.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
O. Dormond, J. C. Madsen, and D. M. Briscoe
The Effects of mTOR-Akt Interactions on Anti-apoptotic Signaling in Vascular Endothelial Cells
J. Biol. Chem., August 10, 2007; 282(32): 23679 - 23686.
[Abstract] [Full Text] [PDF]


Home page
HeartHome page
M. Clarke, M. Bennett, and T. Littlewood
Cell death in the cardiovascular system
Heart, June 1, 2007; 93(6): 659 - 664.
[Abstract] [Full Text] [PDF]


Home page
Physiol. GenomicsHome page
S. Rajan, S. S. Williams, G. Jagatheesan, R. P. H. Ahmed, G. Fuller-Bicer, A. Schwartz, B. J. Aronow, and D. F. Wieczorek
Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy
Physiol Genomics, November 21, 2006; 27(3): 309 - 317.
[Abstract] [Full Text] [PDF]


Home page
Ann. Thorac. Surg.Home page
H. Luckraz, M. Goddard, K. McNeil, C. Atkinson, L. D. Sharples, and J. Wallwork
Is obliterative bronchiolitis in lung transplantation associated with microvascular damage to small airways?
Ann. Thorac. Surg., October 1, 2006; 82(4): 1212 - 1218.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
R. D. Balsara, F. J. Castellino, and V. A. Ploplis
A Novel Function of Plasminogen Activator Inhibitor-1 in Modulation of the AKT Pathway in Wild-type and Plasminogen Activator Inhibitor-1-deficient Endothelial Cells
J. Biol. Chem., August 11, 2006; 281(32): 22527 - 22536.
[Abstract] [Full Text] [PDF]


Home page
Exp. Biol. Med.Home page
S. Jesmin, S. Zaedi, N. Yamaguchi, S. Maeda, I. Yamaguchi, K. Goto, and T. Miyauchi
Effects of dual endothelin receptor antagonist on antiapoptotic marker bcl-2 expression in streptozotocin-induced diabetic rats.
Experimental Biology and Medicine, June 1, 2006; 231(6): 1034 - 1039.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
S. Mattiussi, K. Matsumoto, B. Illi, F. Martelli, M. C. Capogrossi, and C. Gaetano
Papilloma protein E6 abrogates shear stress-dependent survival in human endothelial cells: Evidence for specialized functions of paxillin
Cardiovasc Res, June 1, 2006; 70(3): 578 - 588.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
T. A. Williams, A. Verhovez, A. Milan, F. Veglio, and P. Mulatero
Protective Effect of Spironolactone on Endothelial Cell Apoptosis
Endocrinology, May 1, 2006; 147(5): 2496 - 2505.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
E. Fadel, E. Wijtenburg, R. Michel, J.-X. Mazoit, R. Bernatchez, B. Decante, E. Sage, M. Mazmanian, and P. Herve
Regression of the Systemic Vasculature to the Lung after Removal of Pulmonary Artery Obstruction
Am. J. Respir. Crit. Care Med., February 1, 2006; 173(3): 345 - 349.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
F. Baffert, T. Le, B. Sennino, G. Thurston, C. J. Kuo, D. Hu-Lowe, and D. M. McDonald
Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H547 - H559.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J. Martini, B. Carpentier, A. C. Negrete, J. A. Frangos, and M. Intaglietta
Paradoxical hypotension following increased hematocrit and blood viscosity
Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2136 - H2143.
[Abstract] [Full Text] [PDF]


Home page
Exp PhysiolHome page
P. Madeddu
Therapeutic angiogenesis and vasculogenesis for tissue regeneration
Exp Physiol, May 1, 2005; 90(3): 315 - 326.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
Y.-s. Yoon, S. Uchida, O. Masuo, M. Cejna, J.-S. Park, H.-c. Gwon, R. Kirchmair, F. Bahlman, D. Walter, C. Curry, et al.
Progressive Attenuation of Myocardial Vascular Endothelial Growth Factor Expression Is a Seminal Event in Diabetic Cardiomyopathy: Restoration of Microvascular Homeostasis and Recovery of Cardiac Function in Diabetic Cardiomyopathy After Replenishment of Local Vascular Endothelial Growth Factor
Circulation, April 26, 2005; 111(16): 2073 - 2085.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
F. Tertemiz, U. A. Kayisli, A. Arici, and R. Demir
Apoptosis Contributes to Vascular Lumen Formation and Vascular Branching in Human Placental Vasculogenesis
Biol Reprod, March 1, 2005; 72(3): 727 - 735.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. F. Sun, T. Phung, I. Shiojima, T. Felske, J. N. Upalakalin, D. Feng, T. Kornaga, T. Dor, A. M. Dvorak, K. Walsh, et al.
Microvascular patterning is controlled by fine-tuning the Akt signal
PNAS, January 4, 2005; 102(1): 128 - 133.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
L. V. M. Rao and U. R. Pendurthi
Tissue Factor-Factor VIIa Signaling
Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 47 - 56.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
S. V. Ashton, G. St. J. Whitley, P. R. Dash, M. Wareing, I. P. Crocker, P. N. Baker, and J. E. Cartwright
Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions
Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 102 - 108.
[Abstract] [Full Text] [PDF]


Home page
J EndocrinolHome page
K Horiguchi, S Yagi, K Ono, Y Nishiura, M Tanaka, M Ishida, and T Harigaya
Prolactin gene expression in mouse spleen helper T cells
J. Endocrinol., December 1, 2004; 183(3): 639 - 646.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
D. H.-K. Ma, J.-Y. Yao, L.-K. Yeh, S.-T. Liang, L.-C. See, H.-T. Chen, K.-Y. Lin, C.-C. Liang, K.-K. Lin, and J.-K. Chen
In Vitro Antiangiogenic Activity in Ex Vivo Expanded Human Limbocorneal Epithelial Cells Cultivated on Human Amniotic Membrane
Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2586 - 2595.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
L. B. Pritzker, M. Scatena, and C. M. Giachelli
The Role of Osteoprotegerin and Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Microvascular Endothelial Cell Survival
Mol. Biol. Cell, June 1, 2004; 15(6): 2834 - 2841.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
H. Ohashi, H. Takagi, H. Oh, K. Suzuma, I. Suzuma, N. Miyamoto, A. Uemura, D. Watanabe, T. Murakami, T. Sugaya, et al.
Phosphatidylinositol 3-Kinase/Akt Regulates Angiotensin II-Induced Inhibition of Apoptosis in Microvascular Endothelial Cells by Governing Survivin Expression and Suppression of Caspase-3 Activity
Circ. Res., April 2, 2004; 94(6): 785 - 793.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
C. Emanueli, G. Graiani, M. B. Salis, S. Gadau, E. Desortes, and P. Madeddu
Prophylactic Gene Therapy With Human Tissue Kallikrein Ameliorates Limb Ischemia Recovery in Type 1 Diabetic Mice
Diabetes, April 1, 2004; 53(4): 1096 - 1103.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
T. Bruhl, C. Heeschen, A. Aicher, A. S. Jadidi, J. Haendeler, J. Hoffmann, M. D. Schneider, A. M. Zeiher, S. Dimmeler, and L. Rossig
p21Cip1 Levels Differentially Regulate Turnover of Mature Endothelial Cells, Endothelial Progenitor Cells, and In Vivo Neovascularization
Circ. Res., March 19, 2004; 94(5): 686 - 692.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
S. C. Tai, G. B. Robb, and P. A. Marsden
Endothelial Nitric Oxide Synthase: A New Paradigm for Gene Regulation in the Injured Blood Vessel
Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 405 - 412.
[Abstract] [Full Text]


Home page
Cardiovasc ResHome page
F. Aoudjit and J. Sevigny
P21Waf1/Cip1 in endothelial cell survival
Cardiovasc Res, March 1, 2004; 61(4): 648 - 650.
[Full Text] [PDF]


Home page
Cardiovasc ResHome page
S. Mattiussi, P. Turrini, L. Testolin, F. Martelli, G. Zaccagnini, A. Mangoni, L. M Barlucchi, A. Antonini, B. Illi, C. Cirielli, et al.
p21Waf1/Cip1/Sdi1 mediates shear stress-dependent antiapoptotic function
Cardiovasc Res, March 1, 2004; 61(4): 693 - 704.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
L. Coultas, P. Bouillet, E. G. Stanley, T. C. Brodnicki, J. M. Adams, and A. Strasser
Proapoptotic BH3-Only Bcl-2 Family Member Bik/Blk/Nbk Is Expressed in Hemopoietic and Endothelial Cells but Is Redundant for Their Programmed Death
Mol. Cell. Biol., February 15, 2004; 24(4): 1570 - 1581.
[Abstract] [Full Text] [PDF]


Home page
Infect. Immun.Home page
J. E. Kirby
Anthrax Lethal Toxin Induces Human Endothelial Cell Apoptosis
Infect. Immun., January 1, 2004; 72(1): 430 - 439.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
S.-R. Lee and E. H. Lo
Interactions Between p38 Mitogen-Activated Protein Kinase and Caspase-3 in Cerebral Endothelial Cell Death After Hypoxia-Reoxygenation
Stroke, November 1, 2003; 34(11): 2704 - 2709.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. B. Sorensen, L. V. M. Rao, D. Tornehave, S. Gammeltoft, and L. C. Petersen
Antiapoptotic effect of coagulation factor VIIa
Blood, September 1, 2003; 102(5): 1708 - 1715.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
C. V. Suschek, O. Schnorr, K. Hemmrich, O. Aust, L.-O. Klotz, H. Sies, and V. Kolb-Bachofen
Critical Role of l-Arginine in Endothelial Cell Survival During Oxidative Stress
Circulation, May 27, 2003; 107(20): 2607 - 2614.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
M. Artwohl, W. F. Graier, M. Roden, M. Bischof, A. Freudenthaler, W. Waldhausl, and S. M. Baumgartner-Parzer
Diabetic LDL Triggers Apoptosis in Vascular Endothelial Cells
Diabetes, May 1, 2003; 52(5): 1240 - 1247.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
S.-i. Miura, M. Fujino, Y. Matsuo, A. Kawamura, H. Tanigawa, H. Nishikawa, and K. Saku
High Density Lipoprotein-Induced Angiogenesis Requires the Activation of Ras/MAP Kinase in Human Coronary Artery Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., May 1, 2003; 23(5): 802 - 808.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
S.-i. Miura, Y. Matsuo, and K. Saku
Transactivation of KDR/Flk-1 by the B2 Receptor Induces Tube Formation in Human Coronary Endothelial Cells
Hypertension, May 1, 2003; 41(5): 1118 - 1123.
[Abstract] [Full Text] [PDF]


Home page
Ann. Thorac. Surg.Home page
H. S. Thatte, K. S. Biswas, S. F. Najjar, V. Birjiniuk, M. D. Crittenden, T. Michel, and S. F. Khuri
Multi-photon microscopic evaluation of saphenous vein endothelium and its preservation with a new solution, GALA
Ann. Thorac. Surg., April 1, 2003; 75(4): 1145 - 1152.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
L. Loufrani, B. I. Levy, and D. Henrion
Defect in Microvascular Adaptation to Chronic Changes in Blood Flow in Mice Lacking the Gene Encoding for Dystrophin
Circ. Res., December 13, 2002; 91(12): 1183 - 1189.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
M. Weis, C. L. Schlichting, E. G. Engleman, and J. P. Cooke
Endothelial Determinants of Dendritic Cell Adhesion and Migration: New Implications for Vascular Diseases
Arterioscler. Thromb. Vasc. Biol., November 1, 2002; 22(11): 1817 - 1823.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Hippenstiel, B. Schmeck, P. D. N'Guessan, J. Seybold, M. Krull, K. Preissner, C. V. Eichel-Streiber, and N. Suttorp
Rho protein inactivation induced apoptosis of cultured human endothelial cells
Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L830 - L838.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. Verma, C.-H. Wang, S.-H. Li, A. S. Dumont, P. W.M. Fedak, M. V. Badiwala, B. Dhillon, R. D. Weisel, R.-K. Li, D. A.G. Mickle, et al.
A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis
Circulation, August 20, 2002; 106(8): 913 - 919.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
I. Spyridopoulos, C. Luedemann, D. Chen, M. Kearney, D. Chen, T. Murohara, N. Principe, J. M. Isner, and D. W. Losordo
Divergence of Angiogenic and Vascular Permeability Signaling by VEGF: Inhibition of Protein Kinase C Suppresses VEGF-Induced Angiogenesis, but Promotes VEGF-Induced, NO-Dependent Vascular Permeability
Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 901 - 906.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J.-S. Silvestre, R. Tamarat, T. Senbonmatsu, T. Icchiki, T. Ebrahimian, M. Iglarz, S. Besnard, M. Duriez, T. Inagami, and B. I. Levy
Antiangiogenic Effect of Angiotensin II Type 2 Receptor in Ischemia-Induced Angiogenesis in Mice Hindlimb
Circ. Res., May 31, 2002; 90(10): 1072 - 1079.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Lorenzo, C. Ruiz-Ruiz, A. J. Quesada, G. Hernandez, A. Rodriguez, A. Lopez-Rivas, and J. M. Redondo
Doxorubicin Induces Apoptosis and CD95 Gene Expression in Human Primary Endothelial Cells through a p53-dependent Mechanism
J. Biol. Chem., March 22, 2002; 277(13): 10883 - 10892.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. E. Kirby and D. M. Nekorchuk
Bartonella-associated endothelial proliferation depends on inhibition of apoptosis
PNAS, March 19, 2002; (2002) 72292699.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Weis, C. Heeschen, A. J. Glassford, and J. P. Cooke
Statins Have Biphasic Effects on Angiogenesis
Circulation, February 12, 2002; 105(6): 739 - 745.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
N. Wang and M. B. Stemerman
Ref-1 and Transcriptional Control of Endothelial Apoptosis
Circ. Res., June 22, 2001; 88(12): 1223 - 1225.
[Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
C.-H. Yeh, H.-C. Peng, R.-S. Yang, and T.-F. Huang
Rhodostomin, A Snake Venom Disintegrin, Inhibits Angiogenesis Elicited by Basic Fibroblast Growth Factor and Suppresses Tumor Growth by A Selective alpha vbeta 3 Blockade of Endothelial Cells
Mol. Pharmacol., April 16, 2001; 59(5): 1333 - 1342.
[Abstract] [Full Text]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. E. Kirby and D. M. Nekorchuk
Bartonella-associated endothelial proliferation depends on inhibition of apoptosis
PNAS, April 2, 2002; 99(7): 4656 - 4661.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Biol.Home page
T. Matsumoto, I. Turesson, M. Book, P. Gerwins, and L. Claesson-Welsh
p38 MAP kinase negatively regulates endothelial cell survival, proliferation, and differentiation in FGF-2-stimulated angiogenesis
J. Cell Biol., January 7, 2002; 156(1): 149 - 160.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J. L. Hall, X. Wang, Van Adamson, Y. Zhao, and G. H. Gibbons
Overexpression of Ref-1 Inhibits Hypoxia and Tumor Necrosis Factor-Induced Endothelial Cell Apoptosis Through Nuclear Factor-{kappa}B-Independent and -Dependent Pathways
Circ. Res., June 22, 2001; 88(12): 1247 - 1253.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J. Hoffmann, J. Haendeler, A. Aicher, L. Rossig, M. Vasa, A. M. Zeiher, and S. Dimmeler
Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli: Important Role of Nitric Oxide
Circ. Res., October 12, 2001; 89(8): 709 - 715.
[Abstract] [Full Text] [PDF]