Published online before print April 25, 2002, doi: 10.1161/01.RES.0000019892.41157.24
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 10, 2001
Revised on April 16, 2002
Accepted on April 16, 2002
Antiangiogenic Effect of Angiotensin II Type 2 Receptor in Ischemia-Induced Angiogenesis in Mice Hindlimb
Jean-Sébastien Silvestre ;
From INSERM U541 (J.-S.S., R.T., T.E., M.I., S.B., M.D., B.I.L.), Hôpital Lariboisière, IFR Circulation-Lariboisière, Université Paris 7-Denis Diderot, Paris, France; and the Department of Biochemistry (T.S., T. Icchiki, T. Inagami), Vanderbilt University School of Medicine, Nashville, Tenn.
* To whom correspondence should be addressed. E-mail: levy{at}infobiogen.fr.
This study examined the potential role of angiotensin type 2 (AT2) receptor on angiogenesis in a model of surgically induced hindlimb ischemia. Ischemia was produced by femoral artery ligature in both wild-type and AT2 gene--deleted mice (Agtr2-/Y). After 28 days, angiogenesis was quantitated by microangiography, capillary density measurement, and laser Doppler perfusion imaging. Protein levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Bax, and Bcl-2 were determined by Western blot analysis in hindlimbs. The AT2 mRNA level (assessed by semiquantitative RT-PCR) was increased in the ischemic hindlimb of wild-type mice. Angiographic vessel density and laser Doppler perfusion data showed significant improvement in ischemic/nonischemic leg ratio, 1.9- and 1.7-fold, respectively, in Agtr2-/Y mice compared with controls. In ischemic leg of Agtr2-/Y mice, revascularization was associated with an increase in the antiapoptotic protein content, Bcl-2 (211% of basal), and a decrease (60% of basal) in the number of cell death, determined by TUNEL method. Angiotensin II treatment (0.3 mg/kg per day) raised angiogenic score, blood perfusion, and both VEGF and eNOS protein content in ischemic leg of wild-type control but did not modulate the enhanced angiogenic response observed in untreated Agtr2-/Y mice. Finally, immunohistochemistry analysis revealed that VEGF was mainly localized to myocyte, whereas eNOS-positive staining was mainly observed in the capillary of ischemic leg of both wild-type and AT2-deficient mice. This study demonstrates for the first time that the AT2 receptor subtype may negatively modulate ischemia-induced angiogenesis through an activation of the apoptotic process.
Key words: angiogenesis • ischemia • angiotensin II • AT2 receptor • apoptosis
This article has been cited by other articles:
 |
|
 |
|
  C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera Peptide Hormone Regulation of Angiogenesis Physiol Rev, October 1, 2009; 89(4): 1177 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Leroyer, T. G. Ebrahimian, C. Cochain, A. Recalde, O. Blanc-Brude, B. Mees, J. Vilar, A. Tedgui, B. I. Levy, G. Chimini, et al. Microparticles From Ischemic Muscle Promotes Postnatal Vasculogenesis Circulation, June 2, 2009; 119(21): 2808 - 2817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Suarez and W. C. Sessa MicroRNAs As Novel Regulators of Angiogenesis Circ. Res., February 27, 2009; 104(4): 442 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. I. Ager, J. Neo, and C. Christophi The renin-angiotensin system and malignancy Carcinogenesis, September 1, 2008; 29(9): 1675 - 1684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Herr, M Rodewald, H M Fraser, G Hack, R Konrad, R Kreienberg, and C Wulff Regulation of endothelial proliferation by the renin-angiotensin system in human umbilical vein endothelial cells Reproduction, July 1, 2008; 136(1): 125 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Silvestre, Z. Mallat, A. Tedgui, and B. I. Levy Post-ischaemic neovascularization and inflammation Cardiovasc Res, May 1, 2008; 78(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hu, A. Dandapat, and J. L Mehta Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1 Dependent Redox-Sensitive Pathway Hypertension, November 1, 2007; 50(5): 952 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ribatti, M. T. Conconi, and G. G. Nussdorfer Nonclassic Endogenous Novel Regulators of Angiogenesis Pharmacol. Rev., June 1, 2007; 59(2): 185 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. Munk, L. Sanchez de Miguel, M. Petrimpol, N. Butz, A. Banfi, U. Eriksson, L. Hein, R. Humar, and E. J. Battegay Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT2-B2 Receptor Pathway Hypertension, May 1, 2007; 49(5): 1178 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rakusan, Z. Chvojkova, P. Oliviero, I. Ostadalova, F. Kolar, C. Chassagne, J.-L. Samuel, and B. Ostadal ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1237 - H1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Feihl, L. Liaudet, B. Waeber, and B. I. Levy Hypertension: A Disease of the Microcirculation? Hypertension, December 1, 2006; 48(6): 1012 - 1017. [Full Text] [PDF]
|
|
|
|
|
|
M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Petersen, D. H. Munzenmaier, and A. S. Greene Angiotensin II infusion restores stimulated angiogenesis in the skeletal muscle of rats on a high-salt diet Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H114 - H120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Munzenmaier and A. S. Greene Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H512 - H516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. M. Herrera, L. R. B. Ponce, P. D. Bagamasbad, B. D. VanPelt, T. Didishvili, and N. Ruiz-Opazo Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis Physiol Genomics, November 17, 2005; 23(3): 257 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zheng, I. M. Bird, D.-B. Chen, and R. R. Magness Angiotensin II regulation of ovine fetoplacental artery endothelial functions: interactions with nitric oxide J. Physiol., May 15, 2005; 565(1): 59 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-P. Koh, J.-M. Yuan, D. Van Den Berg, H.-P. Lee, and M. C. Yu Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore Carcinogenesis, February 1, 2005; 26(2): 459 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Watanabe, T. A. Barker, and B. C. Berk Angiotensin II and the Endothelium: Diverse Signals and Effects Hypertension, February 1, 2005; 45(2): 163 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rondelet, F. Kerbaul, R. Van Beneden, S. Motte, P. Fesler, I. Hubloue, M. Remmelink, S. Brimioulle, I. Salmon, J.-M. Ketelslegers, et al. Signaling Molecules in Overcirculation-Induced Pulmonary Hypertension in Piglets: Effects of Sildenafil Therapy Circulation, October 12, 2004; 110(15): 2220 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Duvall, W. Robert Taylor, D. Weiss, and R. E. Guldberg Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H302 - H310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Michel, M.-L. Ambroisine, M. Duriez, C. Delcayre, B. I. Levy, and J.-S. Silvestre Aldosterone Enhances Ischemia-Induced Neovascularization Through Angiotensin II-Dependent Pathway Circulation, April 27, 2004; 109(16): 1933 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ichiki Role of Renin Angiotensin System in Angiogenesis: It Is Still Elusive Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 622 - 624. [Full Text] [PDF]
|
|
|
|
|
|
B. I. Levy Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?: Implications for Therapeutic Blockade of the Renin-Angiotensin System Circulation, January 6, 2004; 109(1): 8 - 13. [Full Text] [PDF]
|
|
|
|
 |
|
 T. WALTHER, A. MENRAD, H.-D. ORZECHOWSKI, G. SIEMEISTER, M. PAUL, and M. SCHIRNER Differential regulation of in vivo angiogenesis by angiotensin II receptors FASEB J, November 1, 2003; 17(14): 2061 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Benndorf, R. H. Boger, S. Ergun, A. Steenpass, and T. Wieland Angiotensin II Type 2 Receptor Inhibits Vascular Endothelial Growth Factor-Induced Migration and In Vitro Tube Formation of Human Endothelial Cells Circ. Res., September 5, 2003; 93(5): 438 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Re Implications of intracrine hormone action for physiology and medicine Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H751 - H757. [Full Text] [PDF]
|
|