Angiotensin-(1-7) and angiotensin-(1-9): Function in cardiac and vascular remodelling

Clinical Science

Volumn 126, Issue 12, 2014, Pages 815-827

  McKinney, Clare A ^a   Fattah, Caroline ^a   Loughrey, Christopher M ^a   Milligan, Graeme ^a   Nicklin, Stuart A ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Angiotensin; Cardiovascular system; Remodelling; Renin Angiotensin System (RAS)

Indexed keywords

ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN CONVERTING ENZYME 2; ANGIOTENSIN DERIVATIVE; ANGIOTENSIN II; ANGIOTENSIN[1-7]; ANGIOTENSIN[1-9]; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; CARDIAC REMODELLING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR SYSTEM; CELL GROWTH; CELL MIGRATION; CELL PROLIFERATION; HEART FAILURE; HUMAN; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; VASCULAR REMODELLING;

ANGIOTENSIN I; HEART; HUMANS; PEPTIDE FRAGMENTS; RENIN-ANGIOTENSIN SYSTEM;

EID: 84895138619     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20130436     Document Type: Review

References (119)

1. Shah, R., Wang, Y. and Foody, J. M. (2008) Effect of statins, angiotensin-converting enzyme inhibitors, and β blockers on survival in patients _65 years of age with heart failure and preserved left ventricular systolic function. Am. J. Cardiol. 101, 217-222
2. Ng, K. K. and Vane, J. R. (1967) Conversion of angiotensin I to angiotensin II. Nature 216, 762-766
3. Cushman, D. W., Cheung, H. S. and Peterson, A. E. (1971) Properties of the angiotensin-converting enzyme of lung. Chest (Suppl.), 10S-11S
4. Bruneval, P., Hinglais, N., Alhenc-Gelas, F., Tricottet, V., Corvol, P., Menard, J., Camilleri, J. P. and Bariety, J. (1986) Angiotensin I converting enzyme in human intestine and kidney. Ultrastructural immunohistochemical localization. Histochemistry 85, 73-80
5. Mehta, P. K. and Griendling, K. K. (2007) Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. Cell Physiol. 292, C82-C97
6. Booz, G. W. and Baker, K. M. (1996) Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy. Hypertension 28, 635-640
7. Nakajima, M., Hutchinson, H. G., Fujinaga, M., Hayashida, W., Morishita, R., Zhang, L., Horiuchi, M., Pratt, R. E. and Dzau, V. J. (1995) The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc. Natl. Acad. Sci. U.S.A. 92, 10663-10667
8. Akishita, M., Horiuchi, M., Yamada, H., Zhang, L., Shirakami, G., Tamura, K., Ouchi, Y. and Dzau, V. J. (2000) Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol. Genomics 2, 13-20
9. Hannan, R. E., Davis, E. A. and Widdop, R. E. (2003) Functional role of angiotensin II AT2 receptor in modulation of AT1 receptor-mediated contraction in rat uterine artery: involvement of bradykinin and nitric oxide. Br. J. Pharmacol. 140, 987-995
10. Katada, J. and Majima, M. (2002) AT2 receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions. Br. J. Pharmacol. 136, 484-491
11. Vickers, C., Hales, P., Kaushik, V., Dick, L., Gavin, J., Tang, J., Godbout, K., Parsons, T., Baronas, E., Hsieh, F., Acton, S., Patane, M., Nichols, A. and Tummino, P. (2002) Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J. Biol. Chem. 277, 14838-14843
12. Harmer, D., Gilbert, M., Borman, R. and Clark, K. L. (2002) Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 532, 107-110
13. Donoghue, M., Hsieh, F., Baronas, E., Godbout, K., Gosselin, M., Stagliano, N., Donovan, M., Woolf, B., Robison, K., Jeyaseelan, R., Breitbart, R. E. and Acton, S. (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 87, E1-E9
14. Tipnis, S. R., Hooper, N. M., Hyde, R., Karran, E., Christie, G. and Turner, A. J. (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 275, 33238-33243
15. Chappell, M. C., Tallant, E. A, Brosnihan, K. B and Ferrario, C. M. (1994) Conversion of angiotensin I to angiotensin-(1-7) by thimet oligopeptidase (EC3.4.24.15) in vascular smooth muscle cells. J. Vasc. Med. Biol. 5, 129-137
16. Rice, G. I., Thomas, D. A., Grant, P. J., Turner, A. J. and Hooper, N. M. (2004) Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem. J. 383, 45-51
17. Yamada, K., Iyer, S. N., Chappell, M. C., Ganten, D. and Ferrario, C. M. (1998) Converting enzyme determines plasma clearance of angiotensin-(1-7). Hypertension 32, 496-502
18. Chappell, M. C., Pirro, N. T., Sykes, A. and Ferrario, C. M. (1998) Metabolism of angiotensin-(1-7) by angiotensin-converting enzyme. Hypertension 31, 362-367
19. Vilas-Boas, W. W., Ribeiro-Oliveira, A., Jr., Pereira, R. M., Ribeiro Rda, C., Almeida, J., Nadu, A. P., Simoes e Silva, A. C. and dos Santos, R. A. (2009) Relationship between angiotensin-(1-7) and angiotensin II correlates with hemodynamic changes in human liver cirrhosis. World J. Gastroenterol. 15, 2512-2519
20. Freeman, E. J., Chisolm, G. M., Ferrario, C. M. and Tallant, E. A. (1996) Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension 28, 104-108
21. Langeveld, B., van Gilst, W. H., Tio, R. A., Zijlstra, F. and Roks, A. J. (2005) Angiotensin-(1-7) attenuates neointimal formation after stent implantation in the rat. Hypertension 45, 138-141
22. Lovren, F., Pan, Y., Quan, A., Teoh, H., Wang, G., Shukla, P. C., Levitt, K. S., Oudit, G. Y., Al-Omran, M., Stewart, D. J., Slutsky, A. S., Peterson, M. D., Backx, P. H., Penninger, J. M. and Verma, S. (2008) Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am. J. Physiol. Heart Circ. Physiol. 295, H1377-H1384
23. Tesanovic, S., Vinh, A., Gaspari, T. A., Casley, D. and Widdop, R. E. (2010) Vasoprotective and atheroprotective effects of angiotensin (1-7) in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 30, 1606-1613
24. Rowe, B. P., Saylor, D. L., Speth, R. C. and Absher, D. R. (1995) Angiotensin-(1-7) binding at angiotensin II receptors in the rat brain. Regul. Pept. 56, 139-146
25. Santos, R. A., Simoes e Silva, A. C., Maric, C., Silva, D. M., Machado, R. P., de Buhr, I., Heringer-Walther, S., Pinheiro, S. V., Lopes, M. T., Bader, M. et al. (2003) Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. U.S.A. 100, 8258-8263
26. Bosnyak, S., Jones, E. S., Christopoulos, A., Aguilar, M. I., Thomas, W. G. and Widdop, R. E. (2011) Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors. Clin. Sci. 121, 297-303
27. Castro, C. H., Santos, R. A., Ferreira, A. J., Bader, M., Alenina, N. and Almeida, A. P. (2005) Evidence for a functional interaction of the angiotensin-(1-7) receptor Mas with AT1 and AT2 receptors in the mouse heart. Hypertension 46, 937-942
28. Walters, P. E., Gaspari, T. A. and Widdop, R. E. (2005) Angiotensin-(1-7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension 45, 960-966
29. Bosnyak, S., Widdop, R. E., Denton, K. M. and Jones, E. S. (2012) Differential mechanisms of ang (1-7)-mediated vasodepressor effect in adult and aged candesartan-treated rats. Int. J. Hypertens. 2012, 192567
30. Gembardt, F., van Veghel, R., Coffman, T. M., Schultheiss, H. P., Danser, A. H. and Walther, T. (2012) Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors. Hypertens. Res. 35, 547-551
31. Jackman, H. L., Massad, M. G., Sekosan, M., Tan, F., Brovkovych, V., Marcic, B. M. and Erdos, E. G. (2002) Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A. Hypertension 39, 976-981
32. Kokkonen, J. O., Saarinen, J. and Kovanen, P. T. (1997) Regulation of local angiotensin II formation in the human heart in the presence of interstitial fluid. Inhibition of chymase by protease inhibitors of interstitial fluid and of angiotensinconverting enzyme by Ang-(1-9) formed by heart carboxypeptidase A-like activity. Circulation 95, 1455-1463
33. Campbell, D. J., Kladis, A. and Duncan, A. M. (1993) Nephrectomy, converting enzyme inhibition, and angiotensin peptides. Hypertension 22, 513-522
34. Ocaranza, M. P., Godoy, I., Jalil, J. E., Varas, M., Collantes, P., Pinto, M., Roman, M., Ramirez, C., Copaja, M., Diaz-Araya, G. et al. (2006) Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat. Hypertension 48, 572-578
35. Turner, A. J., Tipnis, S. R., Guy, J. L., Rice, G. and Hooper, N. M. (2002) ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors. Can. J. Physiol. Pharmacol. 80, 346-353
36. Flores-Munoz, M., Smith, N. J., Haggerty, C., Milligan, G. and Nicklin, S. A. (2011) Angiotensin-1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor. J. Physiol. 589, 939-951
37. Clarke, W. P. and Bond, R. A. (1998) The elusive nature of intrinsic efficacy. Trends Pharmacol. Sci. 19, 270-276
38. Miura, S. and Karnik, S. S. (1999) Angiotensin II type 1 and type 2 receptors bind angiotensin II through different types of epitope recognition. J. Hypertens. 17, 397-404
39. Lautner, R. Q., Villela, D. C., Fraga-Silva, R. A., Silva, N., Verano-Braga, T., Costa-Fraga, F., Jankowski, J., Jankowski, V., Sousa, F., Alzamora, A. et al. (2013) Discovery and characterization of alamandine: a novel component of the renin-angiotensin system. Circ. Res. 112, 1104-1111
40. Selvetella, G., Hirsch, E., Notte, A., Tarone, G. and Lembo, G. (2004) Adaptive and maladaptive hypertrophic pathways: points of convergence and divergence. Cardiovasc. Res. 63, 373-380
41. Domeier, T. L., Blatter, L. A. and Zima, A. V. (2009) Alteration of sarcoplasmic reticulum Ca2+ release termination by ryanodine receptor sensitization and in heart failure. J. Physiol. 587, 5197-5209
42. Schultz Jel, J., Witt, S. A., Glascock, B. J., Nieman, M. L., Reiser, P. J., Nix, S. L., Kimball, T. R. and Doetschman, T. (2002) TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J. Clin. Invest. 109, 787-796
43. Horiguchi, M., Ota, M. and Rifkin, D. B. (2012) Matrix control of transforming growth factor-β function. J. Biochem. 152, 321-329
44. Fomovsky, G. M., Rouillard, A. D. and Holmes, J. W. (2012) Regional mechanics determine collagen fiber structure in healing myocardial infarcts. J. Mol. Cell. Cardiol. 52, 1083-1090
45. Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos Santos, A. J., da Costa, J., Zhang, L., Pei, Y. et al. (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417, 822-828
46. Kassiri, Z., Zhong, J., Guo, D., Basu, R., Wang, X., Liu, P. P., Scholey, J. W., Penninger, J. M. and Oudit, G. Y. (2009) Loss of angiotensin-converting enzyme 2 accelerates maladaptive left ventricular remodeling in response to myocardial infarction. Circ. Heart Fail. 2, 446-455
47. Patel, V. B., Bodiga, S., Basu, R., Das, S. K., Wang, W., Wang, Z., Lo, J., Grant, M. B., Zhong, J., Kassiri, Z. and Oudit, G. Y. (2012) Loss of angiotensin-converting enzyme-2 exacerbates diabetic cardiovascular complications and leads to systolic and vascular dysfunction: a critical role of the angiotensin II/AT1 receptor axis. Circ. Res. 110, 1322-1335
48. Masson, R., Nicklin, S. A., Craig, M. A., McBride, M., Gilday, K., Gregorevic, P., Allen, J. M., Chamberlain, J. S., Smith, G., Graham, D. et al. (2009) Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensinconverting enzyme 2. Hypertension 53, 694-700
49. Donoghue, M., Wakimoto, H., Maguire, C. T., Acton, S., Hales, P., Stagliano, N., Fairchild-Huntress, V., Xu, J., Lorenz, J. N., Kadambi, V. et al. (2003) Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins. J. Mol. Cell. Cardiol. 35, 1043-1053
50. Varagic, J., Ahmad, S., Brosnihan, K. B., Groban, L., Chappell, M. C., Tallant, E. A., Gallagher, P. E. and Ferrario, C. M. (2010) Decreased cardiac Ang-(1-7) is associated with salt-induced cardiac remodeling and dysfunction. Ther. Adv. Cardiovasc. Dis. 4, 17-25
51. Gava, E., de Castro, C. H., Ferreira, A. J., Colleta, H., Melo, M. B., Alenina, N., Bader, M., Oliveira, L. A., Santos, R. A. and Kitten, G. T.. (2012) Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart. Regul. Pept. 175, 30-42
52. Grobe, J. L., Mecca, A. P., Mao, H. and Katovich, M. J. (2006) Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension. Am. J. Physiol. Heart Circ. Physiol. 290, H2417-H2423
53. Ferreira, A. J., Castro, C. H., Guatimosim, S., Almeida, P. W., Gomes, E. R., Dias-Peixoto, M. F., Alves, M. N., Fagundes-Moura, C. R., Rentzsch, B., Gava, E. et al. (2010) Attenuation of isoproterenol-induced cardiac fibrosis in transgenic rats harboring an angiotensin-(1-7)-producing fusion protein in the heart. Ther. Adv. Cardiovasc. Dis. 4, 83-96
54. Santos, R. A., Ferreira, A. J., Nadu, A. P., Braga, A. N., de Almeida, A. P., Campagnole-Santos, M. J., Baltatu, O., Iliescu, R., Reudelhuber, T. L. and Bader, M. (2004) Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats. Physiol. Genomics 17, 292-299
55. Mercure, C., Yogi, A., Callera, G. E., Aranha, A. B., Bader, M., Ferreira, A. J., Santos, R. A., Walther, T., Touyz, R. M. and Reudelhuber, T. L. (2008) Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart. Circ. Res. 103, 1319-1326
56. Qi, Y., Shenoy, V., Wong, F., Li, H., Afzal, A., Mocco, J., Sumners, C., Raizada, M. K. and Katovich, M. J. (2011) Lentivirus-mediated overexpression of angiotensin-(1-7) attenuated ischaemia-induced cardiac pathophysiology. Exp. Physiol. 96, 863-874
57. Iwata, M., Cowling, R. T., Gurantz, D., Moore, C., Zhang, S., Yuan, J. X. and Greenberg, B. H. (2005) Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am. J. Physiol. Heart Circ. Physiol. 289, H2356-H2363
58. McCollum, L. T., Gallagher, P. E. and Tallant, E. A. (2012) Angiotensin-(1-7) abrogates mitogen-stimulated proliferation of cardiac fibroblasts. Peptides 34, 380-388
59. Ferreira, A. J., Shenoy, V., Qi, Y., Fraga-Silva, R. A., Santos, R. A., Katovich, M. J. and Raizada, M. K. (2011) Angiotensinconverting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases. Exp. Physiol. 96, 287-294
60. Zhong, J., Basu, R., Guo, D., Chow, F. L., Byrns, S., Schuster, M., Loibner, H., Wang, X. H., Penninger, J. M., Kassiri, Z. and Oudit, G. Y. (2010) Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Circulation 122, 717-728
61. Zhao, W., Zhao, T., Chen, Y. and Sun, Y. (2013) Angiotensin 1-7 promotes cardiac angiogenesis following infarction. Curr. Vasc. Pharmacol., in the press
62. Costa, M. A., Lopez Verrilli, M. A., Gomez, K. A., Nakagawa, P., Pena, C., Arranz, C. and Gironacci, M. M. (2010) Angiotensin-(1-7) upregulates cardiac nitric oxide synthase in spontaneously hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 299, H1205-H1211
63. Inaba, S., Iwai, M., Furuno, M., Kanno, H., Senba, I., Okayama, H., Mogi, M., Higaki, J. and Horiuchi, M. (2011) Role of angiotensin-converting enzyme 2 in cardiac hypertrophy induced by nitric oxide synthase inhibition. J. Hypertens. 29, 2236-2245
64. Ocaranza, M. P., Lavandero, S., Jalil, J. E., Moya, J., Pinto, M., Novoa, U., Apablaza, F., Gonzalez, L., Hernandez, C., Varas, M. et al. (2010) Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro. J. Hypertens. 28, 1054-1064
65. Flores-Munoz, M., Work, L. M., Douglas, K., Denby, L., Dominiczak, A. F., Graham, D. and Nicklin, S. A. (2012) Angiotensin-(1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertension 59, 300-307
66. Horiuchi, M., Akishita, M. and Dzau, V. J. (1999) Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension 33, 613-621
67. Nouet, S. and Nahmias, C. (2000) Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol. Metab. 11, 1-6
68. Calo, L. A., Schiavo, S., Davis, P. A., Pagnin, E., Mormino, P., A. D'Angelo and Pessina, A. C. (2010) Angiotensin II signaling via type 2 receptors in a human model of vascular hyporeactivity: implications for hypertension. J. Hypertens. 28, 111-118
69. Weber, K. T., Sun, Y., Bhattacharya, S. K., Ahokas, R. A. and Gerling, I. C. (2013) Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat. Rev. Cardiol. 10, 15-26
70. Gusev, K., Domenighetti, A. A., Delbridge, L. M., Pedrazzini, T., Niggli, E. and Egger, M. (2009) Angiotensin II-mediated adaptive and maladaptive remodeling of cardiomyocyte excitation-contraction coupling. Circ. Res. 105, 42-50
71. Loot, A. E., Roks, A. J., Henning, R. H., Tio, R. A., Suurmeijer, A. J., Boomsma, F. and van Gilst, W. H. (2002) Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats. Circulation 105, 1548-1550
72. Gomes, E. R., Lara, A. A., Almeida, P. W., Guimaraes, D., Resende, R. R., Campagnole-Santos, M. J., Bader, M., Santos, R. A. and Guatimosim, S. (2010) Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3_,5_-cyclic monophosphate-dependent pathway. Hypertension 55, 153-160
73. Patel, V. B., Bodiga, S., Fan, D., Das, S. K., Wang, Z., Wang, W., Basu, R., Zhong, J., Kassiri, Z. and Oudit, G. Y. (2012) Cardioprotective effects mediated by angiotensin II type 1 receptor blockade and enhancing angiotensin 1-7 in experimental heart failure in angiotensin-converting enzyme 2-null mice. Hypertension 59, 1195-1203
74. Ferreira, A. J., Santos, R. A. and Almeida, A. P. (2001) Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension 38, 665-668
75. Liao, X., Wang, L., Yang, C., He, J., Wang, X., Guo, R., Lan, A., Dong, X., Yang, Z., Wang, H., Feng, J. and Ma, H. (2011) Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress. Mol. Med. Rep. 4, 1145-1150
76. De Mello, W. C. (2004) Angiotensin (1-7) re-establishes impulse conduction in cardiac muscle during ischaemiareperfusion. The role of the sodium pump. J. Renin Angiotensin Aldosterone. Syst. 5, 203-208
77. Liu, E., Yang, S., Xu, Z., Li, J., Yang, W. and Li, G. (2010) Angiotensin-(1-7) prevents atrial fibrosis and atrial fibrillation in long-term atrial tachycardia dogs. Regul. Pept. 162, 73-78
78. Dias-Peixoto, M. F., Santos, R. A., Gomes, E. R., Alves, M. N., Almeida, P. W., Greco, L., Rosa, M., Fauler, B., Bader, M., Alenina, N. and Guatimosim, S. (2008) Molecular mechanisms involved in the angiotensin-(1-7)/Mas signaling pathway in cardiomyocytes. Hypertension 52, 542-548
79. Wang, Y., Qian, C., Roks, A. J., Westermann, D., Schumacher, S. M., Escher, F., Schoemaker, R. G., Reudelhuber, T. L., van Gilst, W. H., Schultheiss, H. P., Tschope, C. and Walther, T. (2010) Circulating rather than cardiac angiotensin-(1-7) stimulates cardioprotection after myocardial infarction. Circ. Heart Fail. 3, 286-293
80. Chen, J., Xiao, X., Chen, S., Zhang, C., Yi, D., Shenoy, V., Raizada, M. K., Zhao, B. and Chen, Y. (2013) Angiotensinconverting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy. Hypertension 61, 681-689
81. Jarajapu, Y. P., Bhatwadekar, A. D., Caballero, S., Hazra, S., Shenoy, V., Medina, R., Kent, D., Stitt, A. W., Thut, C., Finney, E. M. et al. (2013) Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors. Diabetes 62, 1258-1269
82. Rodgers, K. E., Oliver, J. and diZerega, G. S. (2006) Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer. Cancer Chemother. Pharmacol. 57, 559-568
83. Ross, R. (1999) Atherosclerosis - an inflammatory disease. N. Engl. N. J. Med. 340, 115-126
84. Bryan, A. J. and Angelini, G. D. (1994) The biology of saphenous vein graft occlusion: etiology and strategies for prevention. Curr. Opin. Cardiol. 9, 641-649
85. Hanke, H., Strohschneider, T., Oberhoff, M., Betz, E. and Karsch, K. R. (1990) Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circ. Res. 67, 651-659
86. Newby, A. C. (1997) Molecular and cell biology of native coronary and vein-graft atherosclerosis: regulation of plaque stability and vessel-wall remodelling by growth factors and cell-extracellular matrix interactions. Coron. Artery Dis. 8, 213-224
87. West, N., Guzik, T., Black, E. and Channon, K. (2001) Enhanced superoxide production in experimental venous bypass graft intimal hyperplasia: role of NAD(P)H oxidase. Arterioscler. Thromb. Vasc. Biol. 21, 189-194
88. Galis, Z. S. and Khatri, J. J. (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ. Res. 90, 251-262
89. Libby, P., Schwartz, D., Brogi, E., Tanaka, H. and Clinton, S. K. (1992) A cascade model for restenosis. A special case of atherosclerosis progression. Circulation 86, III47-III52
90. Hunyady, L. and Catt, K. J. (2006) Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol. Endocrinol. 20, 953-970
91. Sluimer, J. C., Gasc, J. M., Hamming, I., van Goor, H., Michaud, A., van den Akker, L. H., Jutten, B., Cleutjens, J., Bijnens, A. P., Corvol, P. et al. (2008) Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions. J. Pathol 215, 273-279
92. Dong, B., Zhang, Y. H., Dong, Q. L., Yu, Q. T., Zhu, L., Li, S. Y., Yang, Y. P., Zhang, C., Feng, J. B., Liu, C. X. et al. (2009) Overexpression of angiotensin converting enzyme 2 inhibits inflammatory response of atherosclerotic plaques in hypercholesterolemic rabbits. Zhonghua Xin Xue Guan Bing Za Zhi 37, 622-625
93. Tallant, E. A., Diz, D. I. and Ferrario, C. M. (1999) Antiproliferative actions of angiotensin-(1-7) in vascular smooth muscle. Hypertension 34, 950-957
94. Zhang, F., Hu, Y., Xu, Q. and Ye, S. (2010) Different effects of angiotensin II and angiotensin-(1-7) on vascular smooth muscle cell proliferation and migration. PLoS ONE 5, e12323
95. Jaiswal, N., Tallant, E. A., Jaiswal, R. K., Diz, D. I. and Ferrario, C. M. (1993) Differential regulation of prostaglandin synthesis by angiotensin peptides in porcine aortic smooth muscle cells: subtypes of angiotensin receptors involved. Pharmacol, J. Exp. Ther. 265, 664-673
96. Strawn, W. B., Ferrario, C. M. and Tallant, E. A. (1999) Angiotensin-(1-7) reduces smooth muscle growth after vascular injury. Hypertension 33, 207-211
97. Zeng, W., Chen, W., Leng, X., He, J. G. and Ma, H. (2009) Chronic angiotensin-(1-7) administration improves vascular remodeling after angioplasty through the regulation of the TGF-β/Smad signaling pathway in rabbits. Biochem. Biophys. Res. Commun. 389, 138-144
98. Yang, J. M., Dong, M., Meng, X., Zhao, Y. X., Yang, X. Y., Liu, X. L., Hao, P. P., Li, J. J., Wang, X. P., Zhang, K. et al. (2013) Angiotensin-(1-7) dose-dependently inhibits atherosclerotic lesion formation and enhances plaque stability by targeting vascular cells. Arterioscler. Thromb. Vasc. Biol. 33, 1978-1985
99. Wiemer, G., Dobrucki, L. W., Louka, F. R., Malinski, T. and Heitsch, H. (2002) AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium. Hypertension 40, 847-852
100. Sheng-Long, C., Yan-Xin, W., Yi-Yi, H., Ming, F., Jian-Gui, H., Yi-Li, C., Wen-Jing, X. and Hong, M. (2012) AVE0991, a nonpeptide compound, attenuates angiotensin II-induced vascular smooth muscle cell proliferation via induction of heme oxygenase-1 and downregulation of p-38 MAPK phosphorylation. Int. J. Hypertens. 2012, 958298
101. Brosnihan, K. B., Li, P. and Ferrario, C. M. (1996) Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension 27, 523-528
102. Faria-Silva, R., Duarte, F. V. and Santos, R. A. (2005) Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats. Hypertension 46, 948-952
103. Sampaio, W. O., Souza dos Santos, R. A., Faria-Silva, R., da Mata Machado, L. T., Schiffrin, E. L. and Touyz, R. M. (2007) Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension 49, 185-192
104. Stegbauer, J., Potthoff, S. A., Quack, I., Mergia, E., Clasen, T., Friedrich, S., Vonend, O., Woznowski, M., Konigshausen, E., Sellin, L. and Rump, L. C. (2011) Chronic treatment with angiotensin-(1-7) improves renal endothelial dysfunction in apolipoprotein E-deficient mice. Br. J. Pharmacol. 163, 974-983
105. Fraga-Silva, R. A., Pinheiro, S. V., Goncalves, A. C., Alenina, N., Bader, M. and Santos, R. A. (2008) The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets. Mol. Med. 14, 28-35
106. Heitsch, H., Brovkovych, S., Malinski, T. and Wiemer, G. (2001) Angiotensin-(1-7)-stimulated nitric oxide and superoxide release from endothelial cells. Hypertension 37, 72-76
107. Uekama, K. (2004) Design and evaluation of cyclodextrin-based drug formulation. Chem. Pharm. Bull. 52, 900-915
108. Fraga-Silva, R. A., Costa-Fraga, F. P., De Sousa, F. B., Alenina, N., Bader, M., Sinisterra, R. D. and Santos, R. A. (2011) An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect. Clinics 66, 837-841
109. Ocaranza, M. P., Rivera, P., Novoa, U., Pinto, M., Gonzalez, L., Chiong, M., Lavandero, S. and Jalil, J. E. (2011) Rho kinase inhibition activates the homologous angiotensin-converting enzyme-angiotensin-(1-9) axis in experimental hypertension. J. Hypertens. 29, 706-715
110. Kramkowski, K., Mogielnicki, A., Leszczynska, A. and Buczko, W. (2010) Angiotensin-(1-9), the product of angiotensin I conversion in platelets, enhances arterial thrombosis in rats. J. Physiol. Pharmacol. 61, 317-324
111. Mogielnicki, A., Chabielska, E., Pawlak, R., Szemraj, J. and Buczko, W. (2005) Angiotensin II enhances thrombosis development in renovascular hypertensive rats. Thromb. Haemost. 93, 1069-1076
112. Kaminska, M., Mogielnicki, A., Stankiewicz, A., Kramkowski, K., Domaniewski, T., Buczko, W. and Chabielska, E. (2005) Angiotensin II via AT1 receptor accelerates arterial thrombosis in renovascular hypertensive rats. J. Physiol. Pharmacol. 56, 571-585
113. Drummer, O. H., Kourtis, S. and Johnson, H. (1988) Formation of angiotensin II and other angiotensin peptides from des-leu 10-angiotensin I in rat lung and kidney. Biochem. Pharmacol. 37, 4327-4333
114. Singh, R., Singh, A. K. and Leehey, D. J. (2005) A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli. Am. J. Physiol. Renal Physiol. 288, F1183-F1190
115. Sampaio, W. O., Henrique de Castro, C., Santos, R. A., Schiffrin, E. L. and Touyz, R. M. (2007) Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension 50, 1093-1098
116. Ray, R., Murdoch, C. E., Wang, M., Santos, C. X., Zhang, M., Alom-Ruiz, S., Anilkumar, N., Ouattara, A., Cave, A. C., Walker, S. J. et al. (2011) Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler. Thromb. Vasc. Biol. 31, 1368-1376
117. Rodrigues-Machado, M. G., Magalhaes, G. S., Cardoso, J. A., Kangussu, L. M., Murari, A., Caliari, M. V., Oliveira, M. L., Cara, D. C., Noviello, M. L., Marques, F. D. et al. (2013) AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma. Br. J. Pharmacol. 170, 835-846
118. Barroso, L. C., Silveira, K. D., Lima, C. X., Borges, V., Bader, M., Rachid, M., Santos, R. A., Souza, D. G., Simoes e Silva, A. C. and Teixeira, M. M. (2012) Renoprotective effects of AVE0991, a nonpeptide mas receptor agonist, in experimental acute renal injury. Int. J. Hypertens. 2012, 808726
119. Ferreira, A. J., Oliveira, T. L., Castro, M. C., Almeida, A. P., Castro, C. H., Caliari, M. V., Gava, E., Kitten, G. T. and Santos, R. A. (2007) Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991. Life Sci. 81, 916-923