Genomes and Genes
Summary: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.
- Cerrato B, Frasch A, Nakagawa P, Longo Carbajosa N, Peña C, Höcht C, et al. Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats. Brain Res. 2012;1453:1-7 pubmed publisher..6-fold increase above basal; SHR: 1.85-fold increase above basal). Our results suggest that Ang-(1-7) upregulates hypothalamic NOS in a hypertensive state as a compensatory and protective mechanism to combat hypertension. ..
- Iwai M, Nakaoka H, Senba I, Kanno H, Moritani T, Horiuchi M. Possible involvement of angiotensin-converting enzyme 2 and Mas activation in inhibitory effects of angiotensin II Type 1 receptor blockade on vascular remodeling. Hypertension. 2012;60:137-44 pubmed publisher..These results suggested that activation of the ACE2-angiotensin-(1-7)-Mas axis is at least partly involved in the beneficial effects of angiotensin II type 1 receptor blockade on vascular remodeling. ..
- Burns W, Velkoska E, Dean R, Burrell L, Thomas M. Angiotensin II mediates epithelial-to-mesenchymal transformation in tubular cells by ANG 1-7/MAS-1-dependent pathways. Am J Physiol Renal Physiol. 2010;299:F585-93 pubmed publisher..This study points to the possible limitations of conventional RAS blockade, which not only fails to antagonize this pathway, but also may enhance it via augmenting the synthesis of ANG 1-7. ..
- Zimmerman M. Angiotensin II and angiotensin-1-7 redox signaling in the central nervous system. Curr Opin Pharmacol. 2011;11:138-43 pubmed publisher..Understanding these intra-neuronal signaling mechanisms should provide insight for the development of new redox-based therapeutics for the improved treatment of angiotensin-dependent neuro-cardiovascular diseases. ..
- Flores Munoz M, Work L, Douglas K, Denby L, Dominiczak A, Graham D, et al. Angiotensin-(1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertension. 2012;59:300-7 pubmed publisher..Angiotensin-converting enzyme 2 metabolizes angiotensin II to angiotensin-(1-7) and angiotensin I to angiotensin-(1-9). Angiotensin-(1-7) antagonizes angiotensin II actions via the receptor Mas...
- Santos S, Braga J, Mario E, Pôrto L, Rodrigues Machado M, Murari A, et al. Improved lipid and glucose metabolism in transgenic rats with increased circulating angiotensin-(1-7). Arterioscler Thromb Vasc Biol. 2010;30:953-61 pubmed publisher..Circulating insulin and muscle glycogen content were not altered in TGR. These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism. ..
- Gomes E, Lara A, Almeida P, Guimarães D, Resende R, Campagnole Santos M, et al. Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway. Hypertension. 2010;55:153-60 pubmed publisher..Taken together, these data reveal a key role for NO/cGMP as a mediator of Ang-(1-7) beneficial effects in cardiac cells. ..
- Pei Z, Meng R, Li G, Yan G, Xu C, Zhuang Z, et al. Angiotensin-(1-7) ameliorates myocardial remodeling and interstitial fibrosis in spontaneous hypertension: role of MMPs/TIMPs. Toxicol Lett. 2010;199:173-81 pubmed publisher..These data indicated the therapeutic potential of angiotensin-(1-7) in spontaneous hypertension-induced cardiac remodeling. ..
- Santiago N, Guimarães P, Sirvente R, Oliveira L, Irigoyen M, Santos R, et al. Lifetime overproduction of circulating Angiotensin-(1-7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling. Hypertension. 2010;55:889-96 pubmed publisher..In addition, DOCA-TG rats showed an important local increase in Ang-(1-7) levels in the LV, which might have contributed to the attenuation of cardiac dysfunction and prefibrotic lesions. ..
- Ehlers P, Nurmi L, Turpeinen A, Korpela R, Vapaatalo H. Casein-derived tripeptide Ile-Pro-Pro improves angiotensin-(1-7)- and bradykinin-induced rat mesenteric artery relaxation. Life Sci. 2011;88:206-11 pubmed publisher..Casein-derived tripeptide Ile-Pro-Pro and amino acid Pro enhance the vasodilatory effect of Ang-(1-7) and bradykinin. The role of ACE2-Ang-(1-7)-Mas axis in the modulation of vascular tone by these compounds seems probable. ..
- Petty W, Miller A, McCoy T, Gallagher P, Tallant E, Torti F. Phase I and pharmacokinetic study of angiotensin-(1-7), an endogenous antiangiogenic hormone. Clin Cancer Res. 2009;15:7398-404 pubmed publisher..04). Ang-(1-7) is a first-in-class antiangiogenic drug with activity for treating cancer that is linked to reduction of plasma PlGF levels. The recommended phase II dose is 400 microg/kg for this administration schedule. ..
- Velez J, Ierardi J, Bland A, Morinelli T, Arthur J, Raymond J, et al. Enzymatic processing of angiotensin peptides by human glomerular endothelial cells. Am J Physiol Renal Physiol. 2012;302:F1583-94 pubmed publisher..Injury to specific cell types within the glomeruli may alter the intrarenal RAS balance. ..
- Samuel P, Ali Q, Sabuhi R, Wu Y, Hussain T. High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT(2)R-MasR axis in obese Zucker rats. Am J Physiol Renal Physiol. 2012;303:F412-9 pubmed publisher..We conclude that such changes may lead to the potentially unopposed function of AT(1)R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension...
- Giani J, Muñoz M, Pons R, Cao G, Toblli J, Turyn D, et al. Angiotensin-(1-7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2011;300:F272-82 pubmed publisher..These results were accompanied with a decrease in both the immunostaining and abundance of IL-6, TNF-?, and NF-?B. In this context, the current study provides strong evidence for a protective role of ANG-(1-7) in the kidney. ..
- Velkoska E, Dean R, Griggs K, Burchill L, Burrell L. Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy. Clin Sci (Lond). 2011;120:335-45 pubmed publisher..Our results add to the increasing evidence that Ang-(1-7) may have deleterious cardiovascular effects in kidney failure and highlight the need for further in vivo studies of the ACE2/Ang-(1-7)/mas receptor axis in kidney disease. ..
- Verma A, Shan Z, Lei B, Yuan L, Liu X, Nakagawa T, et al. ACE2 and Ang-(1-7) confer protection against development of diabetic retinopathy. Mol Ther. 2012;20:28-36 pubmed publisher..Increased expression of ACE2/Ang-(1-7) overcomes this imbalance and confers protection against DR. Thus, strategies enhancing the protective ACE2/Ang-(1-7) axis of RAS in the eye could serve as a novel therapeutic target for DR. ..
- Xu P, Sriramula S, Lazartigues E. ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good. Am J Physiol Regul Integr Comp Physiol. 2011;300:R804-17 pubmed publisher..Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor. ..
- Konoshita T, Makino Y, Kimura T, Fujii M, Wakahara S, Arakawa K, et al. A new-generation N/L-type calcium channel blocker leads to less activation of the renin-angiotensin system compared with conventional L type calcium channel blocker. J Hypertens. 2010;28:2156-60 pubmed publisher..8 ± 16.9/92.9 ± 12.4 mmHg, s-Cr 0.77 ± 0.32 mg/dl, plasma renin activity (PRA) 0.65 ± 0.63 ng/ml per h, angiotensin I (AngI) 70.5 ± 77.3 pg/ml, angiotensin II (AngII) 5.2 ± 3.9 pg/ml, plasma aldosterone concentration (PAC) 76...
- Tesanovic S, Vinh A, Gaspari T, Casley D, Widdop R. Vasoprotective and atheroprotective effects of angiotensin (1-7) in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2010;30:1606-13 pubmed publisher..These effects appear to be mediated by the restoration of nitric oxide bioavailability and involve a complex interaction of both Mas and AT(2) receptors. ..
- da Silveira K, Pompermayer Bosco K, Diniz L, Carmona A, Cassali G, Bruna Romero O, et al. ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats. Clin Sci (Lond). 2010;119:385-94 pubmed publisherAngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (..
- Flores Muñoz M, Smith N, Haggerty C, Milligan G, Nicklin S. Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor. J Physiol. 2011;589:939-51 pubmed publisher..28 ± 0.1). In summary, we ascribe a direct biological role for Ang1-9 acting via the AT2R. This has implications for RAS function and identifying new therapeutic targets in cardiovascular disease. ..
- Stegbauer J, Potthoff S, Quack I, Mergia E, Clasen T, Friedrich S, et al. Chronic treatment with angiotensin-(1-7) improves renal endothelial dysfunction in apolipoproteinE-deficient mice. Br J Pharmacol. 2011;163:974-83 pubmed publisher..Chronic infusion of Ang-(1-7) improved renal endothelial function via Mas receptors, in an experimental model of human cardiovascular disease, by increasing levels of endogenous NO. ..
- Qi Y, Shenoy V, Wong F, Li H, Afzal A, Mocco J, et al. Lentivirus-mediated overexpression of angiotensin-(1-7) attenuated ischaemia-induced cardiac pathophysiology. Exp Physiol. 2011;96:863-74 pubmed publisher..The protective effects of Ang-(1-7) appear to be mediated, at least in part, through modulation of the cardiac renin-angiotensin system and cytokine production. ..
- Ferrario C, Varagic J. The ANG-(1-7)/ACE2/mas axis in the regulation of nephron function. Am J Physiol Renal Physiol. 2010;298:F1297-305 pubmed publisher..This review summarizes the evolving knowledge of the counterregulatory arm of the renin-angiotensin system in the control of nephron function and renal disease. ..
- Trask A, Groban L, Westwood B, Varagic J, Ganten D, Gallagher P, et al. Inhibition of angiotensin-converting enzyme 2 exacerbates cardiac hypertrophy and fibrosis in Ren-2 hypertensive rats. Am J Hypertens. 2010;23:687-93 pubmed publisher..These studies demonstrate that chronic inhibition of ACE2 causes an accumulation of cardiac Ang II, which exacerbates cardiac hypertrophy and fibrosis without having any further impact on blood pressure or cardiac function. ..
- Sukumaran V, Veeraveedu P, Gurusamy N, Yamaguchi K, Lakshmanan A, Ma M, et al. Cardioprotective effects of telmisartan against heart failure in rats induced by experimental autoimmune myocarditis through the modulation of angiotensin-converting enzyme-2/angiotensin 1-7/mas receptor axis. Int J Biol Sci. 2011;7:1077-92 pubmed
- Gwathmey T, Pendergrass K, Reid S, Rose J, Diz D, Chappell M. Angiotensin-(1-7)-angiotensin-converting enzyme 2 attenuates reactive oxygen species formation to angiotensin II within the cell nucleus. Hypertension. 2010;55:166-71 pubmed publisher..We conclude that an ACE2-Ang-(1-7)-AT(7)R pathway modulates Ang II-dependent ROS formation within the nucleus, providing a unique protective mechanism against oxidative stress and cell damage. ..
- Dilauro M, Burns K. Angiotensin-(1-7) and its effects in the kidney. ScientificWorldJournal. 2009;9:522-35 pubmed publisher..by angiotensin-converting enzyme 2 (ACE2)-mediated degradation of Ang II, sequential cleavage of the precursor angiotensin I (Ang I) by ACE2 and ACE, or the actions of brush-border membrane peptidases on Ang I...
- Nakagaki T, Hirooka Y, Ito K, Kishi T, Hoka S, Sunagawa K. Role of angiotensin-(1-7) in rostral ventrolateral medulla in blood pressure regulation via sympathetic nerve activity in Wistar-Kyoto and spontaneous hypertensive rats. Clin Exp Hypertens. 2011;33:223-30 pubmed publisher..Our results suggest that endogenous Ang-(1-7) in the RVLM contributes to maintain AP and renal sympathetic nerve activity both in SHR and WKY and that its activity might be enhanced in SHR. ..
- McCollum L, Gallagher P, Tallant E. Angiotensin-(1-7) abrogates mitogen-stimulated proliferation of cardiac fibroblasts. Peptides. 2012;34:380-8 pubmed publisher..Increased Ang-(1-7) or agents that enhance production of the heptapeptide hormone may prevent abnormal fibrosis that occurs during cardiac pathologies. ..
- Yousif M, Dhaunsi G, Makki B, Qabazard B, Akhtar S, Benter I. Characterization of Angiotensin-(1-7) effects on the cardiovascular system in an experimental model of type-1 diabetes. Pharmacol Res. 2012;66:269-75 pubmed publisher..Collectively, these data shed new insights into the likely mechanism of action through which the ACE2/Ang-(1-7)/Mas receptor axis prevents Type 1 diabetes-induced cardiovascular dysfunction...
- Li P, Zhang F, Zhou Y, Cui B, Han Y. Superoxide anions modulate the effects of angiotensin-(1-7) in the rostral ventrolateral medulla on cardiac sympathetic afferent reflex and sympathetic activity in rats. Neuroscience. 2012;223:388-98 pubmed publisher..The enzyme of NAD(P)H oxidase is a major source of the superoxide anions that modulate the effects of Ang-(1-7) in the RVLM. ..
- Flores Munoz M, Godinho B, Almalik A, Nicklin S. Adenoviral delivery of angiotensin-(1-7) or angiotensin-(1-9) inhibits cardiomyocyte hypertrophy via the mas or angiotensin type 2 receptor. PLoS ONE. 2012;7:e45564 pubmed publisher..This supports applications for this approach for sustained peptide delivery to study molecular effects and potential gene therapeutic actions. ..
- Kramkowski K, Mogielnicki A, Leszczynska A, Buczko W. Angiotensin-(1-9), the product of angiotensin I conversion in platelets, enhances arterial thrombosis in rats. J Physiol Pharmacol. 2010;61:317-24 pubmed..We concluded that Ang-(1-9) exerts an Ang II-like prothrombotic effect due to the conversion to Ang II in the circulatory system of rats and that platelets are involved in this process. ..
- Maniatis N, Balyasnikova I, Metzger R, Castellon M, Visintine D, Schwartz D, et al. Reduced expression of angiotensin I-converting enzyme in caveolin-1 knockout mouse lungs. Microvasc Res. 2010;80:250-7 pubmed publisherReduced lung capillary expression of angiotensin I-converting enzyme (ACE), a key enzyme in cardiovascular pathophysiology, and of caveolin-1, an important regulator of endothelial cell signalling, has been demonstrated in various models ..
- Dilauro M, Zimpelmann J, Robertson S, Genest D, Burns K. Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease. Am J Physiol Renal Physiol. 2010;298:F1523-32 pubmed publisher..In contrast, ANG-(1-7) does not affect albuminuria after (5/6) Nx. We propose that endogenous ACE2 is renoprotective in CKD. ..
- Zhou L, Shi Z, Gao J, Han Y, Yuan N, Gao X, et al. Angiotensin-(1-7) and angiotension II in the rostral ventrolateral medulla modulate the cardiac sympathetic afferent reflex and sympathetic activity in rats. Pflugers Arch. 2010;459:681-8 pubmed publisher..In contrast to Ang II, the effects of Ang-(1-7) are not mediated by AT(1) receptors but by Mas receptors. Mas receptors, but not the AT(1) receptors, in the RVLM are involved in the tonic control of the CSAR. ..
- Wysocki J, Ye M, Rodriguez E, Gonzalez Pacheco F, Barrios C, Evora K, et al. Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension. Hypertension. 2010;55:90-8 pubmed publisher..Increasing ACE2 activity may provide a new therapeutic target in states of Ang II overactivity by enhancing its degradation, an approach that differs from the current focus on blocking Ang II formation and action. ..
- Valdes G, Kaufmann P, Corthorn J, Erices R, Brosnihan K, Joyner Grantham J. Vasodilator factors in the systemic and local adaptations to pregnancy. Reprod Biol Endocrinol. 2009;7:79 pubmed publisher..g. L-arginine, NO donors, VEGF transfection) deserves unravelling the intricate association of vasoactive factors and the systemic and local adaptations to pregnancy. ..
- Moon J, Tanimoto M, Gohda T, Hagiwara S, Yamazaki T, Ohara I, et al. Attenuating effect of angiotensin-(1-7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-A(y)/Ta mice. Am J Physiol Renal Physiol. 2011;300:F1271-82 pubmed publisher..The ACE2-ANG-(1-7)-Mas receptor axis should be investigated as a novel target for treatment of type 2 diabetic nephropathy. ..
- Burgelova M, Kramer H, Teplan V, Thumová M, Cervenka L. Effects of angiotensin-(1-7) blockade on renal function in rats with enhanced intrarenal Ang II activity. Kidney Int. 2005;67:1453-61 pubmed..In contrast, under conditions of endogenous RAS activation due to clipping of the renal artery or to sodium restriction, Ang-(1-7) serves as opponent of the vasoconstrictor actions of Ang II. ..
- Tallant E, Ferrario C, Gallagher P. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005;289:H1560-6 pubmed
- Reudelhuber T. A place in our hearts for the lowly angiotensin 1-7 peptide?. Hypertension. 2006;47:811-5 pubmed
- Greco A, Master R, Fokin A, Baber S, Kadowitz P. Angiotensin-(1-7) potentiates responses to bradykinin but does not change responses to angiotensin I. Can J Physiol Pharmacol. 2006;84:1163-75 pubmed..In the present study, the effects of Ang-(1-7) on responses to BK, BK analogs, angiotensin I (Ang I), and Ang II were investigated in the anesthetized rat. The infusion of Ang-(1-7) (55 pmol/min i.v...
- Raizada M, Ferreira A. ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol. 2007;50:112-9 pubmed
- Nie W, Yan H, Li S, Zhang Y, Yu F, Zhu W, et al. Angiotensin-(1-7) enhances angiotensin II induced phosphorylation of ERK1/2 in mouse bone marrow-derived dendritic cells. Mol Immunol. 2009;46:355-61 pubmed publisher..In conclusion, Ang II stimulates ERK1/2 phosphorylation via AT2 receptor in mouse DC, Ang-(1-7) enhances this effect. Generation of Ang-(1-7) by DC could thereby counteract on the pro-inflammatory function of locally generated Ang II. ..
- Gironacci M, Brosnihan K, Ferrario C, Gorzalczany S, Verrilli M, Pascual M, et al. Increased hypothalamic angiotensin-(1-7) levels in rats with aortic coarctation-induced hypertension. Peptides. 2007;28:1580-5 pubmed..The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process. ..
- Joyner J, Neves L, Granger J, Alexander B, Merrill D, Chappell M, et al. Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol. 2007;293:R169-77 pubmed..However, the decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes during hypertensive pregnancy. ..
- Menon J, Soto Pantoja D, Callahan M, Cline J, Ferrario C, Tallant E, et al. Angiotensin-(1-7) inhibits growth of human lung adenocarcinoma xenografts in nude mice through a reduction in cyclooxygenase-2. Cancer Res. 2007;67:2809-15 pubmed..Because Ang-(1-7), a peptide with antithrombotic properties, reduces growth through activation of a selective AT((1-7)) receptor, our results suggest that the heptapeptide represents a novel treatment for lung cancer by reducing COX-2. ..
- Hocht C, Gironacci M, Mayer M, Schuman M, Bertera F, Taira C. Involvement of angiotensin-(1-7) in the hypothalamic hypotensive effect of captopril in sinoaortic denervated rats. Regul Pept. 2008;146:58-66 pubmed
- Lara L, Correa J, Lavelle A, Lopes A, Caruso Neves C. The angiotensin receptor type 1-Gq protein-phosphatidyl inositol phospholipase Cbeta-protein kinase C pathway is involved in activation of proximal tubule Na+-ATPase activity by angiotensin(1-7) in pig kidneys. Exp Physiol. 2008;93:639-47 pubmed publisher..This effect is similar to that described for angiotensin II, showing for the first time that these compounds could have similar effects in the renal system. ..
- Al Maghrebi M, Benter I, Diz D. Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in diabetic hypertensive rats. Pharmacol Res. 2009;59:263-8 pubmed publisher..Whether potential anti-inflammatory and transcriptional factor changes are directly linked to the cardioprotection produced by Ang-(1-7) in diabetic SHR remains to be determined. ..